Sodium Channel Blockers
Epithelial Sodium Channels
NAV1.5 Voltage-Gated Sodium Channel
NAV1.2 Voltage-Gated Sodium Channel
A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.
NAV1.6 Voltage-Gated Sodium Channel
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
Voltage-Gated Sodium Channels
Ion Channel Gating
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
NAV1.8 Voltage-Gated Sodium Channel
Sodium Channel Agonists
NAV1.1 Voltage-Gated Sodium Channel
A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3.
NAV1.7 Voltage-Gated Sodium Channel
NAV1.4 Voltage-Gated Sodium Channel
A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.
Potassium Channels, Inwardly Rectifying
NAV1.3 Voltage-Gated Sodium Channel
Calcium Channel Blockers
Potassium Channel Blockers
Voltage-Gated Sodium Channel Blockers
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
NAV1.9 Voltage-Gated Sodium Channel
Potassium Channels, Voltage-Gated
Voltage-Gated Sodium Channel beta-1 Subunit
A voltage-gated sodium channel beta subunit abundantly expressed in SKELETAL MUSCLE; HEART; and BRAIN. It non-covalently associates with voltage-gated alpha subunits. Defects in the SCN1B gene, which codes for this beta subunit, are associated with generalized epilepsy with febrile seizures plus, type 1, and Brugada syndrome 5.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
Calcium Channels, L-Type
Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.
Epithelial Sodium Channel Blockers
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
Potassium Channels, Calcium-Activated
Shaker Superfamily of Potassium Channels
Acid Sensing Ion Channels
Voltage-Gated Sodium Channel beta-3 Subunit
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Amino Acid Sequence
Calcium Channels, N-Type
Degenerin Sodium Channels
A family of mechanosensitive sodium channels found primarily in NEMATODES where they play a role in CELLULAR MECHANOTRANSDUCTION. Degenerin sodium channels are structurally-related to EPITHELIAL SODIUM CHANNELS and are named after the fact that loss of their activity results in cellular degeneration.
TRPC Cation Channels
Large-Conductance Calcium-Activated Potassium Channels
Calcium Channels, T-Type
Cyclic Nucleotide-Gated Cation Channels
Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)
Voltage-Gated Sodium Channel beta-4 Subunit
Kv1.2 Potassium Channel
Voltage-Gated Sodium Channel beta-2 Subunit
Epithelial Sodium Channel Agonists
Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)
Kv1.3 Potassium Channel
Ether-A-Go-Go Potassium Channels
A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.
Kv1.1 Potassium Channel
TRPV Cation Channels
Dose-Response Relationship, Drug
Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.
TRPM Cation Channels
Kv1.5 Potassium Channel
Calcium Channel Agonists
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
KCNQ Potassium Channels
Shab Potassium Channels
Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.
Small-Conductance Calcium-Activated Potassium Channels
Kv1.4 Potassium Channel
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Transient Receptor Potential Channels
A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.
A peripheral arterial disease that is characterized by the triad of ERYTHEMA, burning PAIN, and increased SKIN TEMPERATURE of the extremities (or red, painful extremities). Erythromelalgia may be classified as primary or idiopathic, familial or non-familial. Secondary erythromelalgia is associated with other diseases, the most common being MYELOPROLIFERATIVE DISORDERS.
Shaw Potassium Channels
Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.
Shal Potassium Channels
Paralyses, Familial Periodic
A heterogenous group of inherited disorders characterized by recurring attacks of rapidly progressive flaccid paralysis or myotonia. These conditions have in common a mutation of the gene encoding the alpha subunit of the sodium channel in skeletal muscle. They are frequently associated with fluctuations in serum potassium levels. Periodic paralysis may also occur as a non-familial process secondary to THYROTOXICOSIS and other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1481)
G Protein-Coupled Inwardly-Rectifying Potassium Channels
KCNQ2 Potassium Channel
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Long QT Syndrome
A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.
An autosomal dominant defect of cardiac conduction that is characterized by an abnormal ST-segment in leads V1-V3 on the ELECTROCARDIOGRAM resembling a right BUNDLE-BRANCH BLOCK; high risk of VENTRICULAR TACHYCARDIA; or VENTRICULAR FIBRILLATION; SYNCOPAL EPISODE; and possible sudden death. This syndrome is linked to mutations of gene encoding the cardiac SODIUM CHANNEL alpha subunit.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Calcium Channels, P-Type
Kidney Tubules, Collecting
A family of membrane-associated proteins responsible for the attachment of the cytoskeleton. Erythrocyte-related isoforms of ankyrin attach the SPECTRIN cytoskeleton to a transmembrane protein (ANION EXCHANGE PROTEIN 1, ERYTHROCYTE) in the erythrocyte plasma membrane. Brain-related isoforms of ankyrin also exist.
Amino Acid Substitution
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Ryanodine Receptor Calcium Release Channel
A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.
KCNQ3 Potassium Channel
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Intermediate-Conductance Calcium-Activated Potassium Channels
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Delayed Rectifier Potassium Channels
Sequence Homology, Amino Acid
Sodium Dodecyl Sulfate
Calcium Channels, R-Type
Cell Membrane Permeability
Voltage-Dependent Anion Channels
Arthropods of the class ARACHNIDA, order Araneae. Except for mites and ticks, spiders constitute the largest order of arachnids, with approximately 37,000 species having been described. The majority of spiders are harmless, although some species can be regarded as moderately harmful since their bites can lead to quite severe local symptoms. (From Barnes, Invertebrate Zoology, 5th ed, p508; Smith, Insects and Other Arthropods of Medical Importance, 1973, pp424-430)
A clinically diverse group of epilepsy syndromes characterized either by myoclonic seizures or by myoclonus in association with other seizure types. Myoclonic epilepsy syndromes are divided into three subtypes based on etiology: familial, cryptogenic, and symptomatic (i.e., occurring secondary to known disease processes such as infections, hypoxic-ischemic injuries, trauma, etc.).
Inherited myotonic disorders with early childhood onset MYOTONIA. Muscular hypertrophy is common and myotonia may impair ambulation and other movements. It is classified as Thomsen (autosomal dominant) or Becker (autosomal recessive) generalized myotonia mainly based on the inheritance pattern. Becker type is also clinically more severe. An autosomal dominant variant with milder symptoms and later onset is known as myotonia levior. Mutations in the voltage-dependent skeletal muscle chloride channel are associated with the disorders.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Paralysis, Hyperkalemic Periodic
An autosomal dominant familial disorder which presents in infancy or childhood and is characterized by episodes of weakness associated with hyperkalemia. During attacks, muscles of the lower extremities are initially affected, followed by the lower trunk and arms. Episodes last from 15-60 minutes and typically occur after a period of rest following exercise. A defect in skeletal muscle sodium channels has been identified as the cause of this condition. Normokalemic periodic paralysis is a closely related disorder marked by a lack of alterations in potassium levels during attacks of weakness. (Adams et al., Principles of Neurology, 6th ed, p1481)
Why are there so few resistance-associated mutations in insecticide target genes? (1/5144)The genes encoding the three major targets of conventional insecticides are: Rdl, which encodes a gamma-aminobutyric acid receptor subunit (RDL); para, which encodes a voltage-gated sodium channel (PARA); and Ace, which encodes insect acetylcholinesterase (AChE). Interestingly, despite the complexity of the encoded receptors or enzymes, very few amino acid residues are replaced in different resistant insects: one within RDL, two within PARA and three or more within AChE. Here we examine the possible reasons underlying this extreme conservation by looking at the aspects of receptor and/or enzyme function that may constrain replacements to such a limited number of residues. (+info)
Molecular dynamics of the sodium channel pore vary with gating: interactions between P-segment motions and inactivation. (2/5144)Disulfide trapping studies have revealed that the pore-lining (P) segments of voltage-dependent sodium channels undergo sizable motions on a subsecond time scale. Such motions of the pore may be necessary for selective ion translocation. Although traditionally viewed as separable properties, gating and permeation are now known to interact extensively in various classes of channels. We have investigated the interaction of pore motions and voltage-dependent gating in micro1 sodium channels engineered to contain two cysteines within the P segments. Rates of catalyzed internal disulfide formation (kSS) were measured in K1237C+W1531C mutant channels expressed in oocytes. During repetitive voltage-clamp depolarizations, increasing the pulse duration had biphasic effects on the kSS, which first increased to a maximum at 200 msec and then decreased with longer depolarizations. This result suggested that occupancy of an intermediate inactivation state (IM) facilitates pore motions. Consistent with the known antagonism between alkali metals and a component of slow inactivation, kSS varied inversely with external [Na+]o. We examined the converse relationship, namely the effect of pore flexibility on gating, by measuring recovery from inactivation in Y401C+E758C (YC/EC) channels. Under oxidative conditions, recovery from inactivation was slower than in a reduced environment in which the spontaneous YC/EC cross-link is disrupted. The most prominent effects were slowing of a component with intermediate recovery kinetics, with diminution of its relative amplitude. We conclude that occupancy of an intermediate inactivation state facilitates motions of the P segments; conversely, flexibility of the P segments alters an intermediate component of inactivation. (+info)
Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation. (3/5144)Using site-directed fluorescent labeling, we examined conformational changes in the S4 segment of each domain of the human skeletal muscle sodium channel (hSkM1). The fluorescence signals from S4 segments in domains I and II follow activation and are unaffected as fast inactivation settles. In contrast, the fluorescence signals from S4 segments in domains III and IV show kinetic components during activation and deactivation that correlate with fast inactivation and charge immobilization. These results indicate that in hSkM1, the S4 segments in domains III and IV are responsible for voltage-sensitive conformational changes linked to fast inactivation and are immobilized by fast inactivation, while the S4 segments in domains I and II are unaffected by fast inactivation. (+info)
Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate. (4/5144)The actions of the antiepileptic drug topiramate (TPM) on Na+ currents were assessed using whole-cell patch-clamp recordings in dissociated neocortical neurons and intracellular recordings in neocortical slices. Relatively low TPM concentrations (25-30 microM) slightly inhibited the persistent fraction of Na+ current in dissociated neurons and reduced the Na+-dependent long-lasting action potential shoulders, which can be evoked in layer V pyramidal neurons after Ca++ and K+ current blockade. Conversely, the same drug concentrations were ineffective in reducing the amplitude of the fast Na+-dependent action potentials evoked in slices or the peak of transient Na+ (INaf) current evoked in isolated neurons from a physiological holding potential. Consistent INaf inhibition became, however, evident only when the neuronal membrane was kept depolarized to enhance resting Na+ channel inactivation. TPM (100 microM) was ineffective on the voltage dependence of activation but induced a leftward shift of the steady-state INaf inactivation curve. The drug-induced inhibitory effect increased with the duration of membrane depolarization, and the recovery of INaf after long membrane depolarizations was slightly delayed in comparison with that observed under control conditions. The obtained evidence suggests that the anticonvulsant action of TPM may operate by stabilizing channel inactivation, which can be induced by depolarizing events similar to those occurring in chronic epileptic conditions. Concurrently, the slight but significant inhibition of the persistent fraction of the Na+ current, obtained with the application of relatively low TPM concentrations, may contribute toward its anticonvulsant effectiveness by modulating the near-threshold depolarizing events that are sustained by this small current fraction. (+info)
Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers. (5/5144)A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 microM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-delta units [conduction velocity (c.v.) 5-18 m/s] but only 50% (5/10) of slow A-delta units (1.5
In vivo NGF deprivation reduces SNS expression and TTX-R sodium currents in IB4-negative DRG neurons. (6/5144)Recent evidence suggests that changes in sodium channel expression and localization may be involved in some pathological pain syndromes. SNS, a tetrodotoxin-resistant (TTX-R) sodium channel, is preferentially expressed in small dorsal root ganglion (DRG) neurons, many of which are nociceptive. TTX-R sodium currents and SNS mRNA expression have been shown to be modulated by nerve growth factor (NGF) in vitro and in vivo. To determine whether SNS expression and TTX-R currents in DRG neurons are affected by reduced levels of systemic NGF, we immunized adult rats with NGF, which causes thermal hypoalgesia in rats with high antibody titers to NGF. DRG neurons cultured from rats with high antibody titers to NGF, which do not bind the isolectin IB4 (IB4(-)) but do express TrkA, were studied with whole cell patch-clamp and in situ hybridization. Mean TTX-R sodium current density was decreased from 504 +/- 77 pA/pF to 307 +/- 61 pA/pF in control versus NGF-deprived neurons, respectively. In comparison, the mean TTX-sensitive sodium current density was not significantly different between control and NGF-deprived neurons. Quantification of SNS mRNA hybridization signal showed a significant decrease in the signal in NGF-deprived neurons compared with the control neurons. The data suggest that NGF has a major role in the maintenance of steady-state levels of TTX-R sodium currents and SNS mRNA in IB4(-) DRG neurons in adult rats in vivo. (+info)
Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule. (7/5144)While studying the adult rat skeletal muscle Na+ channel outer vestibule, we found that certain mutations of the lysine residue in the domain III P region at amino acid position 1237 of the alpha subunit, which is essential for the Na+ selectivity of the channel, produced substantial changes in the inactivation process. When skeletal muscle alpha subunits (micro1) with K1237 mutated to either serine (K1237S) or glutamic acid (K1237E) were expressed in Xenopus oocytes and depolarized for several minutes, the channels entered a state of inactivation from which recovery was very slow, i.e., the time constants of entry into and exit from this state were in the order of approximately 100 s. We refer to this process as "ultra-slow inactivation". By contrast, wild-type channels and channels with the charge-preserving mutation K1237R largely recovered within approximately 60 s, with only 20-30% of the current showing ultra-slow recovery. Coexpression of the rat brain beta1 subunit along with the K1237E alpha subunit tended to accelerate the faster components of recovery from inactivation, as has been reported previously of native channels, but had no effect on the mutation-induced ultra-slow inactivation. This implied that ultra-slow inactivation was a distinct process different from normal inactivation. Binding to the pore of a partially blocking peptide reduced the number of channels entering the ultra-slow inactivation state, possibly by interference with a structural rearrangement of the outer vestibule. Thus, ultra-slow inactivation, favored by charge-altering mutations at site 1237 in micro1 Na+ channels, may be analogous to C-type inactivation in Shaker K+ channels. (+info)
Tetraethylammonium block of the BNC1 channel. (8/5144)The brain Na+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family. Mutation of a specific residue (Gly430) that lies N-terminal to the second membrane-spanning domain activates BNC1 and converts it from a Na+-selective channel to one permeable to both Na+ and K+. Because all K+ channels are blocked by tetraethylammonium (TEA), we asked if TEA would inhibit BNC1 with a mutation at residue 430. External TEA blocked BNC1 when residue 430 was a Val or a Thr. Block was steeply voltage-dependent and was reduced when current was outward, suggesting multi-ion block within the channel pore. Block was dependent on the size of the quaternary ammonium; the smaller tetramethylammonium blocked with similar properties, whereas the larger tetrapropylammonium had little effect. When residue 430 was Phe, the effects of tetramethylammonium and tetrapropylammonium were not altered. In contrast, block by TEA was much less voltage-dependent, suggesting that the Phe mutation introduced a new TEA binding site located approximately 30% of the way across the electric field. These results provide insight into the structure and function of BNC1 and suggest that TEA may be a useful tool to probe function of this channel family. (+info)
Voltage-gated sodium channel subunit alpha Nav1.6 | definition of Voltage-gated sodium channel subunit alpha Nav1.6 by Medical...
Looking for online definition of Voltage-gated sodium channel subunit alpha Nav1.6 in the Medical Dictionary? Voltage-gated sodium channel subunit alpha Nav1.6 explanation free. What is Voltage-gated sodium channel subunit alpha Nav1.6? Meaning of Voltage-gated sodium channel subunit alpha Nav1.6 medical term. What does Voltage-gated sodium channel subunit alpha Nav1.6 mean?
Voltage-dependent sodium channel function is regulated through membrane mechanics<...
TY - JOUR. T1 - Voltage-dependent sodium channel function is regulated through membrane mechanics. AU - Shcherbatko, Anatoly. AU - Ono, Fumihito. AU - Mandel, Gail. AU - Brehm, Paul. PY - 1999/10. Y1 - 1999/10. N2 - Cut-open recordings from Xenopus oocytes expressing either nerve (PN1) or skeletal muscle (SkM1) Na+ channel α subunits revealed slow inactivation onset and recovery kinetics of inward current. In contrast, recordings using the macropatch configuration resulted in an immediate negative shift in the voltage-dependence of inactivation and activation, as well as time-dependent shifts in kinetics when compared to cut-open recordings. Specifically, a slow transition from predominantly slow onset and recovery to exclusively fast onset and fast recovery from inactivation occurred. The shift to fast inactivation was accelerated by patch excision and by agents that disrupted microtubule formation. Application of positive pressure to cell-attached macropatch electrodes prevented the shift in ...
Molecular cloning and analysis of zebrafish voltage-gated sodium channel beta subunit genes: implications for the evolution of...
Action potential generation in excitable cells such as myocytes and neurons critically depends on voltage-gated sodium channels. In mammals, sodium channels exist as macromolecular complexes that include a pore-forming alpha subunit and 1 or more modulatory beta subunits. Although alpha subunit genes have been cloned from diverse metazoans including flies, jellyfish, and humans, beta subunits have not previously been identified in any non-mammalian species. To gain further insight into the evolution of electrical signaling in vertebrates, we investigated beta subunit genes in the teleost Danio rerio (zebrafish). We identified and cloned single zebrafish gene homologs for beta1-beta3 (zbeta1-zbeta3) and duplicate genes for beta4 (zbeta4.1, zbeta4.2). Sodium channel beta subunit loci are similarly organized in fish and mammalian genomes. Unlike their mammalian counterparts, zbeta1 and zbeta2 subunit genes display extensive alternative splicing. Zebrafish beta subunit genes and their splice variants are
Mus musculus epithelial sodium channel alpha subunit mRNA, complete cd - Nucleotide - NCBI
Opens the Highlight Feature Bar and highlights feature annotations from the FEATURES table of the record. The Highlight Feature Bar can be used to navigate to and highlight other features and provides links to display the highlighted region separately. Links in the FEATURES table will also highlight the corresponding region of the sequence. More... ...
Neuronal growth factor regulation of two different sodium channel types through distinct signal transduction pathways | Journal...
Neuronal growth factors regulate the expression of voltage-activated sodium current in differentiating sympathetic neurons and PC12 cells. We show that, in PC12 cells, the NGF- and FGF-induced sodium current results from increased expression of two distinct sodium channel types. Sodium current results from the rapid induction of a novel sodium channel transcript, also found in peripheral neurons, and from the long term induction of brain type II/IIA mRNA. Expression of the type II/IIA sodium channel requires activation of the cyclic AMP-dependent protein kinase (A-kinase), whereas induction of the peripheral neuron type sodium channel occurs through an A-kinase-independent signal transduction pathway. These findings suggest that the two sodium channel types act in concert to ensure the generation of action potentials during neuronal differentiation. ...
Previously cloned voltage-dependent sodium channels exhibit a high degree of homology to one another and appear to comprise a single multigene family. We have now isolated and characterized cDNAs from both human adult heart and fetal skeletal muscle that encode a sodium channel alpha subunit that exhibits only moderate primary structure identity with other sodium channels and is prominently expressed in both heart and uterus. The approximately 7.2-kilobase cDNA sequence, designated hNav2.1, predicts a 1682-amino acid protein that bears 52%, 49%, and 46% overall identity with sodium channels cloned from rat brain, skeletal muscle, and heart, respectively. Positively charged S4 segments are present in hNav2.1, but there are fewer basic residues in repeat domains 1, 3, and 4 than in other cloned sodium channels. The cloning of hNav2.1 provides evidence for greater evolutionary divergence among voltage-dependent sodium channels and suggests that other sodium channel gene subfamilies may exist. The ...
Nav1.2 - Wikipedia
Navα1.2, also known as the sodium channel, voltage-gated, type II, alpha subunit is a protein that in humans is encoded by the SCN2A gene. Functional sodium channels contain an ion conductive alpha subunit and one or more regulatory beta subunits. Sodium channels which contain the Navα1.2 subunit are called Nav1.2 channels. Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four domains including 24 transmembrane segments and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. It is heterogeneously expressed in the brain, and mutations in this gene have been linked to several seizure disorders. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. Mutations in this ...
Indian Patents. 234877:BIARYL SUBSTITUTED 6-MEMBERED HETEROCYCLES AS SODIUM CHANNEL BLOCKERS
Voltage-gated ion channels allow electrically excitable cells to generate and propagate action potentials and therefore are crucial for nerve and muscle function. Sodium channels play a special role by mediating rapid depolarization, which constitutes the rising phase of the action potential and in turn activates voltage-gated calcium and potassium channels. Voltage-gated sodium channels represent a multigene family. Nine sodium channel subtypes have been cloned and functionally expressed to date. [Clare, J. J., Tate, S. N., Nobbs, M. & Romanes, M. A. Voltage-gated sodium channels as therapeutic targets. Drug Discovery Today 5, 506-520 (2000)]. They are differentially expressed throughout muscle and nerve tissues and show distinct biophysical properties. All voltage-gated sodium channels are characterized by a high degree of selectivity for sodium over other ions and by their voltage-dependent gating. [Catterall, W. A. Structure and function of voltage-gated sodium and calcium channels. Current ...
Abstract P081: Voltage-Gated TTX-Sensitive Nav1.1 Brain Sodium Channels Are Important for Cardiac Contractile Function |...
Background: Mutations in voltage gated brain sodium channel Nav1.1 have been linked to many disorders, including Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). Recent studies have identified TTX- sensitive Nav1.1 brain sodium channels in the SA node and ventricular T-tubules of the heart, though their role in cardiac function is still controversial. We tested the functional significance of Nav1.1 sodium channels in the heart by creating a novel knock-in of human epilepsy GEFS+ mutation SCN1A-R1648H at the Scn1a locus of a C57BL/6J X 129 mouse.. Method: In vivo 2-D echocardiography was performed on 2 week old (juvenile) and 8 week old (adult) wild-type and heterozygote (Scn1aRH/+) mice after extracardiac neuronal block through intraperitoneal injections of atropine and propranolol (2.5mg/kg each). Calcium and contractility studies on adult ventricular cardiomyocytes isolated from the wild type and Scn1aRH/+ mice paced at 0.5Hz were ...
NAV1.5 Voltage-Gated Sodium Channel | Profiles RNS
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function ...
SCN1A sodium voltage-gated channel alpha subunit 1 - Gene - GTR - NCBI
Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5 untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]
Expression of auxiliary beta subunits of sodium channels in primary afferent neurons and the effect of nerve injury | Read by...
Multiple voltage-gated sodium channels are the primary mediators of cell excitability. They are multimers that consist of the pore-forming alpha subunit and auxiliary beta subunits. Although ion permeability and voltage sensing are primarily determined by the alpha subunit, beta subunits are important modulators of sodium channel function. The purpose of this study was to assess the effect of axotomy on the expression of beta subunits (beta(1), beta(2) and beta(3)) and coexpression of Na(v)1.3 and beta(3) subunits in the dorsal root ganglion (DRG). We used sciatic nerve transection models or spared nerve injury (SNI) models in the rat. In reverse transcriptase-polymerase chain reaction analysis, there were no significant differences between contralateral and ipsilateral DRGs of beta(1) and beta(2) mRNA 3 days after axotomy. beta(3) mRNA expression in ipsilateral DRGs increased significantly compared with contralateral DRGs 3 days after axotomy. In in situ hybridization histochemistry, beta(1) ...
Hypermorphic mutation of the voltage-gated sodium channel encoding gene Scn10a causes a dramatic stimulus-dependent...
TY - JOUR. T1 - Hypermorphic mutation of the voltage-gated sodium channel encoding gene Scn10a causes a dramatic stimulus-dependent neurobehavioral phenotype. AU - Blasius, Amanda L.. AU - Dubin, Adrienne E.. AU - Petrus, Matt J.. AU - Lim, Byung Kwan. AU - Narezkina, Anna. AU - Criado, José R.. AU - Wills, Derek N.. AU - Xia, Yu. AU - Moresco, Eva Marie Y. AU - Ehlers, Cindy. AU - Knowlton, Kirk U.. AU - Patapoutian, Ardem. AU - Beutler, Bruce. PY - 2011/11/29. Y1 - 2011/11/29. N2 - The voltage-gated sodium channel Na v1.8 is known to function in the transmission of pain signals induced by cold, heat, and mechanical stimuli. Sequence variants of human Nav1.8 have been linked to altered cardiac conduction. We identified an allele of Scn10a encoding the α-subunit of Na v1.8 among mice homozygous for N-ethyl-N-nitrosourea-induced mutations. The allele creates a dominant neurobehavioral phenotype termed Possum, characterized by transient whole-body tonic immobility induced by pinching the skin at ...
CAP-1A is a novel linker that binds clathrin and the voltage-gated sodium channel Na|sub|v|/sub|1.8 - Fingerprint -...
Fingerprint Dive into the research topics of CAP-1A is a novel linker that binds clathrin and the voltage-gated sodium channel Na,sub,v,/sub,1.8. Together they form a unique fingerprint. ...
Stimulatory action of telmisartan, an antagonist of angiotensin II receptor, on voltage-gated Na ...
TY - JOUR. T1 - Stimulatory action of telmisartan, an antagonist of angiotensin II receptor, on voltage-gated Na + current. T2 - Experimental and theoretical studies. AU - Chang, Tzu Tung. AU - Yang, Chia Jung. AU - Lee, Yu Chi. AU - Wu, Sheng-Nan. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Telmisartan (Tel) is recognized as a non-peptide blocker of AT1R. Whether this agent has any direct effects on ion currents remains unexplored. In whole-cell current recordings, addition of Tel increased the peak amplitude of voltage-gated Na + (Na V ) current (I Na ) accompanied by the increased time constant of I Na inactivation in differentiated NSC-34 motor neuron-like cells. Tel-stimulated INa in these cells is unlinked to either blockade of AT1R or activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). In order to explore how this compound affects the amplitude and kinetics of I Na in neurons, a Hodgkin-Huxley-based (HH-based) model designed to mimic effect of Tel on the functional activities ...
A Mutant of TTX-Resistant Cardiac Sodium Channels with TTX-Sensitive Properties | Science
The cardiac sodium channel α subunit (RHI) is less sensitive to tetrodotoxin (TTX) and saxitoxin (STX) and more sensitive to cadmium than brain and skeletal muscle (µl) isoforms. An RHI mutant, with Tyr substituted for Cys at position 374 (as in µl) confers three properties of TTX-sensitive channels: (i) greater sensitivity to TTX (730-fold); (ii) lower sensitivity to cadmium (28-fold); and (iii) altered additional block by toxin upon repetitive stimulation. Thus, the primary determinant of high-affinity TTX-STX binding is a critical aromatic residue at position 374, and the interaction may take place possibly through an ionized hydrogen bond. This finding requires revision of the sodium channel pore structure that has been previously suggested by homology with the potassium channel.. ...
Gentaur Molecular :EIAab \ hNaN,Homo sapiens,Human,Peripheral nerve sodium channel 5,PN5,SCN11A,SCN12A,Sensory neuron sodium...
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Mutagenetix > Incidental...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with mental retardation, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010 ...
Molecular motions of the outer ring of charge of the sodium channel: Do they couple to slow inactivation?<...
TY - JOUR. T1 - Molecular motions of the outer ring of charge of the sodium channel. T2 - Do they couple to slow inactivation?. AU - Xiong, Wei. AU - Li, Ronald A.. AU - Tian, Yanli. AU - Tomaselli, Gordon F.. PY - 2003/9/1. Y1 - 2003/9/1. N2 - In contrast to fast inactivation, the molecular basis of sodium (Na) channel slow inactivation is poorly understood. It has been suggested that structural rearrangements in the outer pore mediate slow inactivation of Na channels similar to C-type inactivation in potassium (K) channels. We probed the role of the outer ring of charge in inactivation gating by paired cysteine mutagenesis in the rat skeletal muscle Na channel (rNav1.4). The outer charged ring residues were substituted with cysteine, paired with cysteine mutants at other positions in the external pore, and coexpressed with rat brain β 1 in Xenopus oocytes. Dithiolthreitol (DTT) markedly increased the current in E403C+E758C double mutant, indicating the spontaneous formation of a disulfide ...
Case-control association study of polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B...
Authors: Larry Baum, Batoul Sadat Haerian, Ho-Keung Ng, Virginia CN Wong, Ping Wing Ng, Colin HT Lui, Ngai Chuen Sin, Chunbo Zhang, Brian Tomlinson, Gary Wing-Kin Wong, Hui Jan Tan, Azman Ali Raymond, Zahurin Mohamed, Patrick Kwan
Sodium channels and pain<...
TY - JOUR. T1 - Sodium channels and pain. AU - Waxman, S. G.. AU - Dib-Hajj, S.. AU - Cummins, T. R.. AU - Black, J. A.. PY - 1999/7/6. Y1 - 1999/7/6. N2 - Although it is well established that hyperexcitability and/or increased baseline sensitivity of primary sensory neurons can lead to abnormal burst activity associated with pain, the underlying molecular mechanisms are not fully understood. Early studies demonstrated that, after injury to their axons, neurons can display changes in excitability, suggesting increased sodium channel expression, and, in fact, abnormal sodium channel accumulation has been observed at the lips of injured axons. We have used an ensemble of molecular, electrophysiological, and pharmacological techniques to ask: what types of sodium channels underlie hyperexcitability of primary sensory neurons after injury? Our studies demonstrate that multiple sodium channels, with distinct electrophysiological properties, are encoded by distinct mRNAs within small dorsal root ...
Mutations in Sodium Channel β1- and β2-Subunits Associated With Atrial FibrillationCLINICAL PERSPECTIVE | Circulation:...
Background- We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF). We also have reported that SCN1B is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel β-subunit genes SCN1B-SCN4B contribute to AF susceptibility.. Methods and Results- Screening for mutations in the 4 β-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant β-subunits on SCN5A mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 ...
British Library EThOS: Pharmacological studies of voltage-gated sodium channel expression in human breast cancer cells :...
The overall aim of this PhD was to improve our understanding, including the clinical potential, of neonatal Nav1.5 (nNav1.5) expression in human metastatic breast cancer. Mainly, the strongly metastatic MDA-MB-231 cells were used throughout the studies. The specific aims were threefold, as follows: 1) To test the effects of several types of voltage-gated sodium channel (VGSC) blocker on nNav1.5 mRNA and protein expression and metastatic cell behaviours (MCBs); (2) to determine the effects of hypoxia on the drug treatments and MCBs; and (3) to elucidate a possible association of carbonic anhydrase-9 (CA9) and nNav1.5 expression/activity. There are three main Results chapters. Results-1 demonstrates the effects of the drugs on MCBs of MDA-MB-231 cells under normal oxygen level (normoxia). Two classes of blocker were used: a) Local anaesthetics (lidocaine and procaine) and (b) blockers of persistent current (INaP) (ranolazine and riluzole). In addition, a specific VGSC blocker, tetrodotoxin (TTX), ...
The Relationship Between Voltage-Gated Sodium Channel Inactivation Fir by J. F. Atherton, A. J. Gillies et al.
Atherton, J. F., Gillies, A. J., Corbett, A. M., & Arbuthnott, G. W. (1998). The Relationship Between Voltage-Gated Sodium Channel Inactivation Firing Frequency in the Subthalamic Nucleus Projection Neuron. European Journal of Neuroscience, 10 (Supplement 10), 300 ...
Birkbeck Institutional Research Online
Voltage-gated sodium channels are important targets for the development of pharmaceutical drugs, because mutations in different human sodium channel isoforms have causal relationships with a range of neurological and cardiovascular diseases. In this study, functional electrophysiological studies show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds and is inhibited by eukaryotic sodium channel blockers in a manner similar to the human Nav1.1 channel, despite millions of years of divergent evolution between the two types of channels. Crystal complexes of the NavMs pore with several brominated blocker compounds depict a common antagonist binding site in the cavity, adjacent to lipid-facing fenestrations proposed to be the portals for drug entry. In silico docking studies indicate the full extent of the blocker binding site, and electrophysiology studies of NavMs channels with mutations at adjacent residues validate the location. These results suggest that the NavMs ...
PC-PLC | PARP inhibitor BMN-673 targeting of the mutant p53-PARP-MCM chromatin axis
Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. isoform predominantly expressed within the peripheral nervous system) is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic currents. Animal studies have shown a decline in Nav1.5 leading to a lower life expectancy action potential upstroke during stage 0. Furthermore, the scholarly study of human tissue shows an inverse expression of sodium channel isoforms; reduced amount of Nav1.5 and enhance of Nav1.8 in both heart failing and ventricular hypertrophy. This strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the SCH 54292 ic50 diseased heart. Targeting aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging research. This review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through SCH 54292 ic50 the ...
The Batrachotoxin Receptor on the Voltage-Gated Sodium Channel is Guarded by the Channel Activation Gate | Molecular...
Batrachotoxin (BTX), from South American frogs of the genusPhyllobates, irreversibly activates voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In this study, we introduced a series of mutations at this site in the Nav1.3 sodium channel, expressed wild-type and mutant channels inXenopus laevis oocytes, and examined their sensitivity to BTX using voltage clamp recording. We found that substitution of either alanine or isoleucine strongly reduced channel sensitivity to toxin, whereas cysteine, tyrosine, or tryptophan decreased toxin action only modestly. These data suggest an electrostatic ligand-receptor interaction at this site, possibly involving a charged tertiary amine on BTX. We then used a mutant channel (mutant F1710C) with intermediate toxin sensitivity to examine the properties of the toxin-receptor reaction in more detail. In ...
SCN3B - Sodium channel subunit beta-3 precursor - Homo sapiens (Human) - SCN3B gene & protein
Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with NFASC may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).
Lubeluzole is widely reported as a multitarget drug acting at least on voltage-gated calcium and sodium channels. There are, however, only a very few studies reporting direct demonstration of sodium channel blockade by lubeluzole in neuronal and cardiac cells (Osikowska-Evers et al., 1995; Le Grand et al., 2003). The more complete study by Le Grand et al., (2003) described the block of sodium channels in single guinea pig ventricular myocytes. It was shown that lubeluzole produces a concentration-dependent tonic and use-dependent block of cardiac sodium channels in a manner similar to that of class I antiarrhythmic drugs, suggesting a greater affinity for inactivated than for resting channels. In the present study, we observed a similar local anesthetic-like effect of lubeluzole on human skeletal muscle sodium channels, and definitely demonstrated that the drug is a very potent blocker of inactivated sodium channels compared with resting channels. The IC50 values calculated for skeletal muscle ...
Rare Genetic Disorder: Sodium channels
Voltage-gated sodium channels play a critical role in the generation and conduction of action potentials - so important for electrical signalling by most excitable cells. Sodium channels are integral membrane proteins and are comprised of a large α subunit, which forms the voltage-sensitive and ion-selective pore, and smaller auxiliary β subunit(s) that can modulate the kinetics and voltage dependence of channel gating. Till 2007, 9 isoforms of the sodium-channel α subunit (Nav1.1- Nav1.9), each with a unique central and peripheral nervous system distribution had been identified. 4 closely related sodium channels (Nav 1.1, -1.2, -1.3, and -1.7) are encoded by a set of 4 genes (SCN1A, SCN2A, SCN3A, and SCN9A, respectively) located within a cluster on chromosome 2q24.3. Mutations in the genes encoding Nav1.1, -1.2, and -1.3 are responsible for a group of epilepsy syndromes with overlapping clinical characteristics but divergent clinical severity, mutation in the gene encoding Nav1.7 has a ...
Sodium channel blocking agent legal definition of sodium channel blocking agent
Definition of sodium channel blocking agent in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is sodium channel blocking agent? Meaning of sodium channel blocking agent as a legal term. What does sodium channel blocking agent mean in law?
Sodium channel β subunits: emerging targets in channelopathies
Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Although β subunits were originally termed auxiliary, we now know that they are multifunctional …
Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers | LE STUDIUM
Voltage-gated sodium channels (NaV) are plasma membrane ion channels that physiological activity is critical for cellular electricity and the functioning of cells characterized as being
Ca <sup>2+</sup> -dependent...
TY - JOUR. T1 - Ca 2+ -dependent regulation of sodium channels Na V 1.4 and Na V 1.5 is controlled by the post-IQ motif AU - Yoder, Jesse B.. AU - Ben-Johny, Manu. AU - Farinelli, Federica. AU - Srinivasan, Lakshmi. AU - Shoemaker, Sophie R.. AU - Tomaselli, Gordon F.. AU - Gabelli, Sandra B.. AU - Amzel, L. Mario. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Skeletal muscle voltage-gated Na + channel (Na V 1.4) activity is subject to calmodulin (CaM) mediated Ca 2+ -dependent inactivation; no such inactivation is observed in the cardiac Na + channel (Na V 1.5). Taken together, the crystal structures of the Na V 1.4 C-terminal domain relevant complexes and thermodynamic binding data presented here provide a rationale for this isoform difference. A Ca 2+ -dependent CaM N-lobe binding site previously identified in Na V 1.5 is not present in Na V 1.4 allowing the N-lobe to signal other regions of the Na V 1.4 channel. Consistent with this mechanism, removing this binding site in Na V 1.5 unveils robust Ca ...
Long QT syndrome (LQT) is an inherited cardiac disorder that causes syncope, seizures and sudden death from ventricular tachyarrhythmias. We used single-strand conformation polymorphism (SSCP) and DNA sequence analyses to identify mutations in the cardiac sodium channel gene, SCN5A, in affected members of four LQT families. These mutations include two identical intragenic deletions and two missense mutations. These data suggest that SCN5A mutations cause LQT. The location and character of these mutations suggest that this form of LQT results from a delay in cardiac sodium channel fast inactivation or altered voltage-dependence of inactivation. ...
Sodium channel biophysics, late sodium current and genetic arrhythmic syndromes. - Oxford Neuroscience
Arrhythmias arise from breakdown of orderly action potential (AP) activation, propagation and recovery driven by interactive opening and closing of successive voltage-gated ion channels, in which one or more Na+ current components play critical parts. Early peak, Na+ currents (I Na) reflecting channel activation drive the AP upstroke central to cellular activation and its propagation. Sustained late Na+ currents (I Na-L) include contributions from a component with a delayed inactivation timecourse influencing AP duration (APD) and refractoriness, potentially causing pro-arrhythmic phenotypes. The magnitude of I Na-L can be analysed through overlaps or otherwise in the overall voltage dependences of the steady-state properties and kinetics of activation and inactivation of the Na+ conductance. This was useful in analysing repetitive firing associated with paramyotonia congenita in skeletal muscle. Similarly, genetic cardiac Na+ channel abnormalities increasing I Na-L are implicated in triggering
JCI - Sodium channel mutations in epilepsy and other neurological disorders
Since the first mutations of the neuronal sodium channel SCN1A were identified 5 years ago, more than 150 mutations have been described in patients with epilepsy. Many are sporadic mutations and cause loss of function, which demonstrates haploinsufficiency of SCN1A. Mutations resulting in persistent sodium current are also common. Coding variants of SCN2A, SCN8A, and SCN9A have also been identified in patients with seizures, ataxia, and sensitivity to pain, respectively. The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well.. ...
SCN7A - Wikipedia
Sodium channel protein type 7 subunit alpha is a protein that in humans is encoded by the SCN7A gene on the chromosome specifically located at 2q21-23 chromosome site. This is one of 10 Sodium channel types, and is expressed in the heart, the uterus and in glial cells. Its sequence identity is 48, and it is the only sodium channel known to be completely un-blockable by TTX (tetrodotoxin). Sodium channel Scn7a is the name of the gene that encodes to a membrane protein, in particular a Sodium Channel Nax (also known as NaG, Nav2.1, etc.) It belongs to a family of Sodium Channel known as Voltage-Gated, but is not activated by changes in the membranes voltage, as happen usually in the members of this family (Nav1.1 to Nav1.9); it activates by changes in the extracellular concentration of sodium [~150 mM]. GRCh38: Ensembl release 89: ENSG00000136546 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000034810 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Plummer NW, ...
Asian Science Citation Index - Articles written by B. S Donahue
Background- We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF). We also have reported that SCN1B is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel β-subunit genes SCN1B-SCN4B contribute to AF susceptibility.. Methods and Results- Screening for mutations in the 4 β-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant β-subunits on SCN5A mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 ...
para - Sodium channel protein - Drosophila melanogaster (Fruit fly) - para gene & protein
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
A gating hinge in Na<sup>+</sup> channels: A molecular switch for electrical...
TY - JOUR. T1 - A gating hinge in Na+ channels. T2 - A molecular switch for electrical signaling. AU - Zhao, Yong. AU - Yarov-Yarovoy, Vladimir. AU - Scheuer, Todd. AU - Catterall, William A.. PY - 2004/3/25. Y1 - 2004/3/25. N2 - Voltage-gated sodium channels are members of a large family with similar pore structures. The mechanism of opening and closing is unknown, but structural studies suggest gating via bending of the inner pore helix at a glycine hinge. Here we provide functional evidence for this gating model for the bacterial sodium channel NaChBac. Mutation of glycine 219 to proline, which would strongly favor bending of the α helix, greatly enhances activation by shifting its voltage dependence -51 mV and slowing deactivation by 2000-fold. The mutation also slows voltage-dependent inactivation by 1200-fold. The effects are specific because substitutions of proline at neighboring positions and substitutions of other amino acids at position 219 have much smaller functional effects. Our ...
PROPERTIES OF 185TAGE-ACTIVATED IONIC CURRENTS IN CELLS FROM THE BRAINS OF THE TRICLAD FLATWORM BDELLOURA CANDIDA | Journal of...
Cells were dispersed from the brains of the triclad flatworm Bdelloura candida and maintained in primary culture for up to 2 weeks. Cultured cells assumed a variety of morphologies consistent with those of neurones in vivo. Whole-cell voltage-clamp recordings from cultured cells revealed that these cells possess a variety of ionic currents, including a fast transient sodium current, a calcium current and several potassium currents. The sodium current does not inactivate completely but instead decays to a steady-state component which has the same physiology and pharmacology as the fast transient component, suggesting that the two components are carried by the same population of channels. The physiology and pharmacology of these various currents were not remarkable save for the fact that, contrary to earlier reports, all sodium currents examined were sensitive to tetrodotoxin (TTX). These animals are, therefore, the lowest animals known to possess TTX-sensitive sodium currents and, as such, ...
Distinct Subcellular Localization of Different Sodium Channel α and β Subunits in Single Ventricular Myocytes From Mouse Heart ...
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Expression of the sodium channel beta3 subunit in injured human sensory neurons. - Oxford Cardiovascular Science
Voltage-gated sodium channel alpha-subunits play a key role in pain pathophysiology, and are modulated by beta-subunits. We previously reported that beta1- and beta2-subunits were decreased in human sensory neurons after spinal root avulsion injury. We have now detected, by immunohistochemistry, beta3-subunits in 82% of small/medium and 67% of large diameter sensory neurons in intact human dorsal root ganglia: 54% of beta3 small/medium neurons were NGF receptor trkA negative. Unlike beta1- and beta2, beta3-immunoreactivity did not decrease after avulsion injury, and the beta3:neurofilament ratio was significantly increased in proximal injured human nerves. beta3-subunit expression may thus be regulated differently from beta1, beta2 and Nav1.8. Targeting beta3 interactions with key alpha-subunits, particularly Nav1.3 and Nav1.8, may provide novel selective analgesics.
Epicardial Border Zone Overexpression of Skeletal Muscle Sodium Channel SkM1 Normalizes Activation, Preserves Conduction, and...
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Int J Dev Biol - Dual roles of voltage-gated sodium channels in development and cancer
Voltage-gated Na+ channels (VGSCs) are heteromeric protein complexes containing pore-forming ? subunits together with non-pore-forming ? subunits. There are nine ? subunits, Nav1.1-Nav1.9, and four ? subunits, ?1-?4. The ? subunits are multifunctional, modulating channel activity, cell surface expression, and are members of the immunoglobulin superfamily of cell adhesion molecules. VGSCs are classically responsible for action potential initiation and conduction in electrically excitable cells, including neurons and muscle cells. In addition, through the ?1 subunit, VGSCs regulate neurite outgrowth and pathfinding in the developing central nervous system. Reciprocal signalling through Nav1.6 and ?1 collectively regulates Na+ current, electrical excitability and neurite outgrowth in cerebellar granule neurons. Thus, ? and ? subunits may have diverse interacting roles dependent on cell/tissue type. VGSCs are also expressed in non-excitable cells, including cells derived from a number of types of cancer. In
Gambierol acts as a functional antagonist of neurotoxin site 5 on voltage-gated sodium channels in cerebellar granule neurons<...
TY - JOUR. T1 - Gambierol acts as a functional antagonist of neurotoxin site 5 on voltage-gated sodium channels in cerebellar granule neurons. AU - LePage, K. T.. AU - Rainier, J. D.. AU - Johnson, H. W.B.. AU - Baden, D. G.. AU - Murray, Thomas F.. PY - 2007/10/1. Y1 - 2007/10/1. N2 - The marine toxin gambierol, a polyether ladder toxin derived from the marine dinoflagellate Gambierdiscus toxicus, was evaluated for interaction with voltage-gated sodium channels (VGSCs) in cerebellar granule neuron (CGN) cultures. At concentrations ranging from 10 nM to 10 μM, gambierol alone had no effect on the intracellular Ca2+ concentration [Ca 2+]i of exposed CGN cultures. Furthermore, there was no evidence of neurotoxicity in CGN cultures exposed for 2 h to gambierol (1 nM-10 μM). However, gambierol was a potent inhibitor (IC50 = 189 nM) of the elevation of [Ca2+]i that accompanies exposure of CGN cultures to the VGSC activator brevetoxin-2 (PbTx-2). To further explore the potential interaction of ...
Provocation of an Autoimmune Response to Cardiac Voltage-Gated Sodium Channel NaV1.5 Induces Cardiac Conduction Defects in Rats...
To study the effect of autoimmunity against the alpha subunit of cardiac voltage-gated sodium channel NaV1.5 in vivo, an autoimmune response was induced in rats through immunization with a NaV1.5-peptide. Consequently, high levels of autoantibodies targeting the third extracellular loop of the first domain could be detected in blood, reflecting successful immunization. Immunized animals developed an exclusively electrical phenotype with conduction defects on the sinoatrial and the atrioventricular level without signs of structural heart disease or myocardial inflammation. On the cellular level, this phenotype is probably caused by a reduced density of INa in cardiomyocytes.. The NaV1.5 is composed of 4 structurally homologous domains (DI-DIV) each consisting of 6 transmembrane segments (S1-S6) (14). The residues between S5 and S6 form the channel pore (P loop) and control ion selectivity and permeation. We chose a peptide sequence between S5 and S6 within the third extracellular loop (residues ...
Neuronal voltage-gated sodium channel subtypes: Key roles in inflammatory and neuropathic pain<...
TY - JOUR. T1 - Neuronal voltage-gated sodium channel subtypes. T2 - Key roles in inflammatory and neuropathic pain. AU - Ekberg, J.. AU - Adams, David J.. PY - 2006. Y1 - 2006. N2 - Voltage-gated sodium channels (VGSCs) play an important role in neuronal excitability. Regulation of VGSC activity is a complex phenomenon that occurs at multiple levels in the cell, including transcriptional regulation, post-translational modification and membrane insertion and retrieval. Multiple VGSC subtypes exist that vary in their biophysical and pharmacological properties and tissue distribution. Any alteration of the VGSC subtype profile of a neuron or the mechanisms that regulate VGSC activity can cause significant changes in neuronal excitability. Inflammatory and neuropathic pain states are characterised by alterations in VGSC subtype composition and activity in sensory neurons. This review focuses on the VGSC subtypes involved in such pain states.. AB - Voltage-gated sodium channels (VGSCs) play an ...
Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia | Journal of Medical...
Two point linkage analysis yielded a maximum lod score (Zmax) of 2.11 at θ = 0 for both markers D2S2370 and D2S2330. Critical recombination events occurring in individual II-3 and III-1 indicate that marker D2S2345 defines the telomeric end. This marker and marker D2S2370, which is reported by the literature7 as the centromeric boundary, limit the responsible gene to a region of 5.98 cM (fig 2). Individual III-5 (3 years old) carried the risk haplotype but was clinically unaffected, possibly due to the late onset of the disease, because all of the affected individuals in this family first showed symptoms at 7-15 years old, and we have not found patients less than 5 years old in the literature.3,8. This genomic interval contains a cluster of sodium channel genes including SCN1A, SCN2A, SCN3A, SCN7A, and SCN9A. Primary erythermalgia can be evoked by various stimulations, comparable to sodium channel diseases such as severe myoclonic epilepsy in infancy (MIM 607208), which is caused by a SCN1A ...
Polymorphism H558R in the human cardiac sodium channel SCN5A g...
Polymorphism H558R in the human cardiac sodium channel SCN5A gene is associated with atrial fibrillation.: Atrial fibrillation (AF) is one of the most common su
Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells. | Circulation Research
We studied the relation of the maximal upstroke velocity (Vmax) of action potentials to the peak sodium current (INa) under voltage clamp in single, internally perfused, canine cardiac Purkinje cells under conditions that ensured membrane action potentials due only to INa. Three different methods of altering sodium channel availability were investigated: voltage-dependent inactivation, tetrodotoxin (TTX) block, and use-dependent block by quinidine. Under all three conditions, the relation of Vmax to INa was nonlinear, and no relation was found that would allow prediction of INa results from Vmax measurements. With voltage-dependent inactivation or TTX block, sodium channel availability measured by Vmax was reduced less than availability measured by peak INa, so that Vmax overestimated sodium channel availability. This overestimation of sodium channel availability by Vmax could be attributed to greater sodium channel mobilization during the slowed action potential upstrokes. The overestimation ...
Bisphenol A Binds to the Local Anesthetic Receptor Site to Block the Human Cardiac Sodium Channel
Bisphenol A (BPA) has attracted considerable public attention as it leaches from plastic used in food containers, is detectable in human fluids and recent epidemiologic studies link BPA exposure with diseases including cardiovascular disorders. As heart-toxicity may derive from modified cardiac electrophysiology, we investigated the interaction between BPA and hNav1.5, the predominant voltage-gated sodium channel subtype expressed in the human heart. Electrophysiology studies of heterologously-expressed hNav1.5 determined that BPA blocks the channel with a Kd of 25.4±1.3 µM. By comparing the effects of BPA and the local anesthetic mexiletine on wild type hNav1.5 and the F1760A mutant, we demonstrate that both compounds share an overlapping binding site. With a key binding determinant thus identified, an homology model of hNav1.5 was generated based on the recently-reported crystal structure of the bacterial voltage-gated sodium channel NavAb. Docking predictions position both ligands in a cavity
Interplay between R513 methylation and S516 phosphorylation of the cardiac voltage-gated sodium channel
Arginine methylation is a novel post-translational modification within the voltage-gated ion channel superfamily, including the cardiac sodium channel, Nav1.5. We show that Nav1.5 R513 methylation decreases S516 phosphorylation rate by 4 orders of magnitude, the first evidence of protein kinase A inhibition by arginine methylation. Reciprocally, S516 phosphorylation blocks R513 methylation. Nav1.5 p.G514C, associated to cardiac conduction disease, abrogates R513 methylation, while leaving S516 phosphorylation rate unchanged. This is the first report of methylation-phosphorylation cross-talk of a cardiac ion channel[-] ...
Operational mechanism of the acid-sensing ion channel that recognizes internal body pain - Scienmag: Latest Science and Health...
Inside the organism, changes in pH levels occur under pathophysiological conditions such as inflammation, ischemia, cancer, and the like, which are accompanied by pain. The Acid-sensing Ion Channel (ASIC) detects changes in pH levels in the organism and transmits the pain signal to the brain. Biologically, many studies have been conducted regarding the Acid-sensing Ion Channel; however, many areas are still unclear, especially in terms of the operational mechanism and the cell membrane merging mechanism. Professor Suhs research team detected the cell membrane merging mechanisms that modulate the activity of the Acid-sensing Ion Channel at the molecular level, and it is this discovery and identification of the new cell membrane merging mechanism of the Acid-sensing Ion Channel that had remained unknown until now. The research team identified through animal experiments that there is a different cell membrane merging mechanism between subunits of the Acid-sensing Ion Channel. ASIC2a can be merged ...
Adelaide Research & Scholarship: The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel
The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in fluid and electrolyte homeostasis and consists of alpha, beta, and gamma subunits. The carboxyl terminus of each ENaC subunit contains a PPxY, motif which is believed to be important for interaction with the WW domains of the ubiquitin-protein ligase, Nedd4. Disruption of this interaction, as in Liddles syndrome, where mutations delete or alter the PPxY motif of either the beta or gamma subunits, has been proposed to result in increased ENaC activity. Here we present evidence that KIAA0439 protein, a close relative of Nedd4, is also a potential regulator of ENaC. We demonstrate that KIAA0439 WW domains bind all three ENaC subunits. We show that a recombinant KIAA0439 WW domain protein acts as a dominant negative mutant that can interfere with the Na(+)-dependent feedback inhibition of ENaC in whole-cell patch clamp experiments. We propose that KIAA0439 and Nedd4 proteins either play a redundant role in ENaC ...
Serval - Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance.
Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet. In Scnn1a(KO) mice, however, this salt restriction-induced increase in ∆PDamil did not occur, and the circadian rhythm of ∆PDamil was blunted. Plasma and urinary sodium and potassium did not change with regular or high-salt diets or potassium loading in control or Scnn1a(KO) mice. However, Scnn1a(KO) mice fed a low-salt diet lost significant amounts of sodium in their feces and exhibited high plasma aldosterone and increased urinary sodium retention. Mice la
A sodium channel blocker, pilsicainide, produces atrial post-repolarization refractoriness through the reduction of sodium...
TY - JOUR. T1 - A sodium channel blocker, pilsicainide, produces atrial post-repolarization refractoriness through the reduction of sodium channel availability. AU - Fukuda, Koji. AU - Watanabe, Jun. AU - Yagi, Takuya. AU - Wakayama, Yuji. AU - Nakano, Makoto. AU - Kondo, Masateru. AU - Kumagai, Koji. AU - Miura, Masahito. AU - Shirato, Kunio. AU - Shimokawa, Hiroaki. PY - 2011/9/2. Y1 - 2011/9/2. N2 - Atrial fibrillation (AF) is the most common tachyarrhythmia. Shortening of atrial action potential duration (APD) and effective refractory period (ERP) is one of the crucial factors in the occurrence and maintenance of AF. ERP is usually shorter than APD, but ERP can be prolonged beyond action potential repolarization in some situations. It is termed as post-repolarization refractoriness (PRR) that is thought to be one of main anti-arrhythmic mechanisms of class I sodium channel blockers (SCBs). Most of anti-arrhythmic agents, including SCBs, have multi-channel blocking effects. It is unknown ...
NAV1.1 Voltage-Gated Sodium Channel | Profiles RNS
A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3 ...
Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral...
Dive into the research topics of Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral ischemia. Together they form a unique fingerprint. ...
Frontiers | MiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats | Frontiers in...
Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs) are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we discovered that SCN3A is the major target of miR-30b, and we then determined whether miR-30b regulated the expression of Nav1.3 by transfecting miR-30b agomir through the stimulation of TNF-α or by transfecting miR-30b antagomir in primary dorsal root ganglion (DRG) neurons. The spinal nerve ligation (SNL) model was used to determine the contribution of miR-30b to neuropathic pain, to evaluate changes in Nav1.3 mRNA and protein expression, and to understand the sensitivity of rats to mechanical and thermal stimuli. Our results showed that miR-30b agomir transfection down-regulated Nav1.3 mRNA stimulated with TNF
Asian Science Citation Index - Articles written by A. V Eliseenkova
Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel binding in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs ...
Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes<...
TY - JOUR. T1 - Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes. AU - Dibas, Adnan. AU - Millar, John Cameron. AU - Al-Farra, Abraham. AU - Yorio, Thomas. PY - 2018/7/3. Y1 - 2018/7/3. N2 - Purpose: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs) after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of ASIC1a provides RGC neuroprotection. Methods: Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. RGC function was measured by Pattern electroretinography (PERG). In addition, retinal ASIC1a and ASIC2 were observed by immunohistochemistry and western blot. Changes in calpain, fodrin, heat shock protein 70 (HSP70), Brn3a, super oxide dismutase-1 (SOD1), catalase, and ...
Fibroblast growth factor homologous factor 2 ( FHF2): gene structure, expression and mapping to the Börjeson-Forssman-Lehmann...
Börjeson-Forssman-Lehmann syndrome (BFLS) is a syndromal X-linked mental retardation, which maps by linkage to the q26 region of the human X chromosome. We have identified a male patient with BFLS-lik
Sodium channels amplify spine potentials - Academic Commons
Dendritic spines mediate most excitatory synapses in the brain. Past theoretical work and recent experimental evidence have suggested that spines could contain sodium channels. We tested this by measuring the effect of the sodium channel blocker tetrodotoxin (TTX) on depolarizations generated by two-photon uncaging of glutamate on spines from mouse neocortical pyramidal neurons. In practically all spines examined, uncaging potentials were significantly reduced by TTX. This effect was postsynaptic and spatially localized to the spine and occurred with uncaging potentials of different amplitudes and in spines of different neck lengths. Our data confirm that spines from neocortical pyramidal neurons are electrically isolated from the dendrite and indicate that they have sodium channels and are therefore excitable structures. Spine sodium channels could boost synaptic potentials and facilitate action potential backpropagation.
Voltage-Gated Sodium Channel Nav1.7 Maintains the Membrane Potential and Regulates the Activation and Chemokine-Induced...
Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a− and CD1a+ DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a− and CD1a+ immature DC (IDC) showed that the frequency of cells expressing Na+ current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a+ cells than in their CD1a− counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (−8.7 ± 1.5 mV) in CD1a+ IDC as compared with CD1a− cells lacking Nav1.7 (−47 ± 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca2+ levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a+ IDC, resulting in decreased ...
ModelDB: Action Potential initiation and backpropagation in Neocortical L5 Pyramidal Neuron (Hu et al. 2009)
This directory contains the Neuron source code for cortical Layer 5 pyramidal cell model and experiments employed in: Distinct Contributions of Na(V)1.6 and Na(V)1.2 in Action Potential Initiation and Backpropagation Wenqin Hu, Cuiping Tian, Tun Li, Mingpo Yang, Han Hou & Yousheng Shu (2009) Nat Neurosci 12(8): 996-1002. Part of model is based on: Mainen, Z. F. and Sejnowski, T. J. Nature 382: 363-6 (1996) Yu, Y., Shu, Y., et al. J Neurosci 28: 7260-72 (2008) Shu, Y., Hasenstaub, A., et al. Nature 441: 761-5. (2006) =============================================== BRIEF OVERVIEW OF THE CONTENTS Three different but related models are involved in this package: 1). A realistic model of Layer 5 pyramidal cell with sophisticatedly described voltage-dependent sodium channels at the axon initial segment. Either action potentials initiation site (figure not shown in the aforementioned paper, see its main text) or backpropagation failure threshold (Supplementary Fig.4 and Fig.8) can be tested here. This ...
Marine Drugs | Free Full-Text | µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic...
The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of amino acids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain
Ca2+ CaM with human cardiac Na+ channel (NaV1.5) inactivation gate | NIH 3D Print Exchange
Enhanced Understanding of Ca2+ Modulation of the Human Cardiac Sodium Channel: Tight Binding of Calmodulin to the Inactivation ...
Novel molecular determinants in the pore region of sodium channels regulate local anesthetic binding<...
TY - JOUR. T1 - Novel molecular determinants in the pore region of sodium channels regulate local anesthetic binding. AU - Yamagishi, Toshio. AU - Xiong, Wei. AU - Kondratiev, Andre. AU - Vélez, Patricio. AU - Méndez-Fitzwilliam, Ailsa. AU - Balser, Jeffrey R.. AU - Marbán, Eduardo. AU - Tomaselli, Gordon F.. PY - 2009/10. Y1 - 2009/10. N2 - The pore of the Na+ channel is lined by asymmetric loops formed by the linkers between the fifth and sixth transmembrane segments (S5-S6). We investigated the role of the N-terminal portion (SS1) of the S5-S6 linkers in channel gating and local anesthetic (LA) block using site-directed cysteine mutagenesis of the rat skeletal muscle (NaV1.4) channel. The mutants examined have variable effects on voltage dependence and kinetics of fast inactivation. Of the cysteine mutants immediately N-terminal to the putative DEKA selectivity filter in four domains, only Q399C in domain I and F1236C in domain III exhibit reduced use-dependent block. These two mutations ...
Voltage-gated sodium channels, which initiate action potentials in mammalian brain neurons, are modulated functionally by cAMP-dependent protein kinase A (PKA), resulting in reduced sodium current amplitude. Comparing brain and muscle sodium channels, we show that only the brain channel is modulated by PKA. The brain sodium channel I-II linker is both necessary and sufficient for PKA modulation, as shown by exchanging the I-II linker regions of the two channels. PKA consensus sites in the brain channel I-II linker were eliminated by deletion and site-specific mutagenesis. The mutant channels demonstrated decreased levels of phosphorylation when metabolically labeled in oocytes with [gamma-32P]-ATP, and they did not respond with a reduction in current magnitude after PKA induction. Modulation of the brain channel by PKA phosphorylation was mimicked by adding fixed negative charges at the PKA consensus sites, suggesting that the decrease in current was a direct result of the negative charge at one ...
Expression and purification of the alpha subunit of the epithelial sodium channel, ENaC
2015 Elsevier Inc. The epithelial sodium channel (ENaC) plays a critical role in maintaining Na+ homeostasis in various tissues throughout the body. An understanding of the structure of the ENaC subunits has been developed from homology modeling based on the related acid sensing ion channel 1 (ASIC1) protein structure, as well as electrophysiological approaches. However, ENaC has several notable functional differences compared to ASIC1, thereby providing justification for determination of its three-dimensional structure. Unfortunately, this goal remains elusive due to several experimental challenges. Of the subunits that comprise a physiological hetero-trimeric αβγENaC, the α-subunit is unique in that it is capable of forming a homo-trimeric structure that conducts Na+ ions. Despite functional and structural interest in αENaC, a key factor complicating structural studies has been its interaction with multiple other proteins, disrupting its homogeneity. In order to address this issue, a ...
An emerging antiarrhythmic target: Late sodium current<...
TY - JOUR. T1 - An emerging antiarrhythmic target. T2 - Late sodium current. AU - Banyasz, T.. AU - Szentandrássy, N.. AU - Magyar, J.. AU - Szabo, Z.. AU - Nánási, P. P.. AU - Chen-Izu, Ye. AU - Izu, Leighton T. PY - 2015/1/1. Y1 - 2015/1/1. N2 - The cardiac late sodium current (INa,L) has been in the focus of research in the recent decade. The first reports on the sustained component of voltage activated sodium current date back to the seventies, but early studies interpreted this tiny current as a product of a few channels that fail to inactivate, having neither physiologic nor pathologic implications. Recently, the cardiac INa,L has emerged as a potentially major arrhythmogenic mechanism in various heart diseases, attracting the attention of clinicians and researchers. Research activity on INa,L has exponentially increased since Ranolazine, an FDA-approved antianginal drug was shown to successfully suppress cardiac arrhythmias by inhibiting INa,L. This review aims to summarize and discuss ...
A-887826 is a structurally novel, potent and voltage-dependent Na(v)1.8 sodium channel blocker that attenuates neuropathic...
A-887826 is a structurally novel, potent and voltage-dependent Na(v)18 sodium channel blocker that attenuates neuropathic tactile allodynia in rats | Laser spine institute london ontariopost_content%%
Patent US7772458 - Animal model for chronic obstructive pulmonary disease and cystic fibrosis - Google Patents
A nonhuman transgenic mammal is described whose genome comprises a promoter construct operably linked to a heterologous DNA encoding an epithelial sodium channel β subunit, wherein said promoter construct directs expression of the epithelial sodium channel β subunit in lung epithelial cells of said animal, and wherein said transgenic mammal has increased lung mucus retention as compared to the corresponding wild-type mammal. The animal is useful in screening compounds for activity in treating lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.
201 Age-Associated Decline in Nav1.4 and Nav1.5 Isoforms of the Sodium Channel in Rat Heart | Heart
Voltage-gated sodium channels (VGSCs) generate the Na+ current (INa) responsible for the cardiac action potential upstroke largely due to the cardiac isoform Nav1.5, but other isoforms are responsible for ˜20% of the upstroke and a component of a sustained sodium current. This sustained component has been attributed with an increasing arrhythmia risk, particularly within the elderly and has been the target of development for new anti-arrhythmic drugs. Our study has investigated the age-associated changes in protein density and localisation of the VGSC alpha-subunits Nav1.5 and Nav1.4 in the rat heart.. Rats at 6, 12 and 28 months of age were sacrificed, their hearts dissected into the regions of left and right ventricle, left and right atria, epicardium and endocardium (n = 5). These regions were analysed by western blot to determine the protein expression of Nav1.5 and Nav1.4 (Alomone, Israel), normalised to the expression of desmin (Dako, UK). Immunocytochemistry of single cardiac myocytes ...
neuroscience - What happens when the conductance of a sodium channel increases? - Biology Stack Exchange
No, not quite. You are on the right lines, but incorrect in thinking that intracellular sodium concentration is higher. At the resting phase of a neuron, there is less sodium inside the cell and more sodium outside the cell. An ATPase sodium potassium pump is constantly pumping 3 sodium ions outside the cell for every 2 potassium cells that enter the cell. For voltage gated sodium channels to open, there must be a significant change in voltage, which can be triggered by the binding of neurotransmitter to receptors for example. This triggers the sodium channels open and sodium will flood into the cell due to a high concentration gradient (because there are more sodium outside than inside) but also due to an electrical gradient (the neuron is more negative on the inside; positive sodium ions will be attracted to the inside).. Because sodium is flooding into the cell, this will cause the membrane potential to become more positive (depolarised) and will eventually reach an action potential (30mV). ...
De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study
Cases of alleged vaccine encephalopathy could in fact be a genetically determined epileptic encephalopathy that arose de novo. These findings have important clinical implications for diagnosis and management of encephalopathy and, if confirmed in other cohorts, major societal implications for the ge …
The role of retromer in the epithelial sodium channel trafficking pathway
The epithelial sodium channel (ENaC) is a protein located at the apical membrane of polarised epithelial cells, primarily expressed in the epithelia of the gastrointestinal tract, lungs and kidney. ENaCs main function is that of absorbing sodium and it is strongly involved in regulating and maintaining total-body salt and water homeostasis, acting as the rate-limiting step for sodium reabsorption into the body. Its activity, therefore, is crucial for determining blood volume and, as a consequence, blood pressure. The sorting and trafficking of ENaC to the apical membrane is a tightly controlled process, requiring the interaction of multiple proteins and organelles. Although ENaC has been well-characterised, there are certain aspects about its trafficking which need to be clarified, such as defining the many proteins involved in the recycling of the channel to and from the apical membrane. A potential, novel candidate involved in ENaC recycling is the retromer complex. This endosome-associated ...
Mapping of voltage sensor positions in resting and inactivated mammali by Tomoya Kubota, Thomas Durek et al.
Voltage-gated sodium channels (Navs) play crucial roles in excitable cells. Although vertebrate Nav function has been extensively studied, the detailed structural basis for voltage-dependent gating mechanisms remain obscure. We have assessed the structural changes of the Nav voltage sensor domain using lanthanide-based resonance energy transfer (LRET) between the rat skeletal muscle voltage-gated sodium channel (Nav1.4) and fluorescently labeled Nav1.4-targeting toxins. We generated donor constructs with genetically encoded lanthanide-binding tags (LBTs) inserted at the extracellular end of the S4 segment of each domain (with a single LBT per construct). Three different Bodipy-labeled, Nav1.4-targeting toxins were synthesized as acceptors: β-scorpion toxin (Ts1)-Bodipy, KIIIA-Bodipy, and GIIIA-Bodipy analogs. Functional Nav-LBT channels expressed in Xenopus oocytes were voltage-clamped, and distinct LRET signals were obtained in the resting and slow inactivated states. Intramolecular distances computed
NOS1-dependent negative feedback regulation of the epithelial sodium channel in the collecting duct.
NOS1-dependent negative feedback regulation of the epithelial sodium channel in the collecting duct. Am J Physiol Renal Physiol. 2014 Nov 12;:ajprenal.00596.2013 Authors: Hyndman KA, Bugaj V, Mironova E, Stockand JD, Pollock JS Abstract With an increase in urine flow there is a significant increase in shear stress against the renal epithelium including the inner medullary col...
Synthesis and biological activity of 7 8 di hydro batrachotoxinin derivatives interacting with fast sodium channels -...
Elin E.A.; Grishin E.V.; Leonov V.N.; Prosolova T.K.; Soldatov N.M.; Torgov I.V.; Myasoedov N.F.; Shevchenko V.P., 1983: Synthesis and biological activity of 7 8 di hydro batrachotoxinin derivatives interacting with fast sodium channels
Westlake Institute for Advanced Study
These authors contributed equally. # Corresponding author). 1.Shen H*, Li Z*, Jiang Y*, Pan X*, Wu J, Cristofori-Armstrong B, Smith JJ, Chin YKY, Lei J, Zhou Q#, King GF#, Yan N#. Structural basis for the modulation of voltage-gated sodium channels by animal toxins. Science (New York, NY). 2018.. 2.Zhou Q#, Zhou N, Wang HW#. Particle segmentation algorithm for flexible single particle reconstruction. Biophys Rep. 2017;3(1):43-55.. 3.Yan Z*, Zhou Q*, Wang L*, Wu J*, Zhao Y, Huang G, et al. Structure of the Nav1.4-beta1 Complex from Electric Eel. Cell. 2017;170(3):470-82 e11.. 4.Shen H*, Zhou Q*, Pan X*, Li Z*, Wu J*, Yan N. Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution. Science (New York, NY). 2017;355(6328).. 5.Gong X*, Qian HW*, Zhou XH*, Wu JP*, Wan T*, Cao PP, Huang WY, Zhao X, Wang X, Wang P, Shi Y, Gao GF, Zhou Q#, Yan N#. Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection. Cell. ...
Sodium channel and clathrin linker elisa and antibody
Shop Sodium channel and clathrin linker ELISA Kit, Recombinant Protein and Sodium channel and clathrin linker Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
gap junction channel activity. Cellular component. • cytoplasm. • integral component of membrane. • gap junction. • cell ... Connexins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and ... Typically the GJB1 protein forms channels through the myelin to the internal Schwann cell or oligodendrocyte, allowing ...
Sodium channel. Voltage-gated. *SCN1A *Familial hemiplegic migraine 3. *GEFS+ 2. *Febrile seizure 3A ...
Thyrotoxic periodic paralysis
... sodium and potassium) across cell membranes. The main ones are the L-type calcium channel α1-subunit and potassium inward ... and sodium channel protein type 4 subunit alpha (Na41.4). ... Sodium channel. Voltage-gated. *SCN1A *Familial hemiplegic ... The condition has been linked with genetic mutations in genes that code for certain ion channels that transport electrolytes ( ... Genetic mutations in the L-type calcium channel α1-subunit (Cav1.1) have been described in Southern Chinese with TPP. The ...
Sodium channel. Voltage-gated. *SCN1A *Familial hemiplegic migraine 3. *GEFS+ 2. *Febrile seizure 3A ...
Some are responsible for other proteins that form part of the sodium channel, known as sodium channel β subunits (SCN1B, SCN2B ... NaV1.5 - α subunit of the cardiac sodium channel carrying the sodium current INa. ... NaVβ3 - β-3 subunit of the cardiac sodium channel carrying the sodium current INa. ... NaVβ2 - Beta-2 subunit of the cardiac sodium channel carrying the sodium current INa. ...
... sodium channels, "SCN3A"). Autism. Patients with autism have overall higher levels of cortical gyrification, but ... "Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development". Neuron. 99 (5): 905- ...
They are fast-acting axonic excitotoxins, which affect the voltage-gated sodium channels. The sodium channels are ... There are many different forms of sodium channels: in mammals, nine different sodium channel 𝛼-subunits have been identified ( ... This results in persistent and prolonged activation of sodium channels and inflow of sodium, which is lethal to the insect. ... and deltamethrin on rat Nav1.6 sodium channels". Toxicology and Applied Pharmacology. 247 (3): 229-237. doi:10.1016/j.taap. ...
Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel ... Because of this role in altering the threshold potential, Nav1.9 is considered a threshold channel. Though most sodium channels ... and has been associated with slower channel kinetics than the tetrodotoxin-sensitive sodium channels. In Nav1.9, this is mostly ... Voltage-gated sodium channels are membrane protein complexes that play a fundamental role in the rising phase of the action ...
Epithelial sodium channel blockers: amiloride and triamterene.. Calcium-sparing diuretics. The term "calcium-sparing ... Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels 5 ... Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. ... This is large in comparison to normal renal sodium reabsorption which leaves only about 0.4% of filtered sodium in the urine. ...
The specific sodium channel isoforms on which bactridine 1 acts are not yet known. Bactridines act on sodium channels in ... They exclusively target sodium channels. Bactridines are unique in that this scorpion toxin acts on sodium channels of both ... In bacteria, bactridines cause an outward sodium leak by increasing the sodium channel permeability. In contrast, as an attack ... Bactridine 1-2 also fall under the sodium channel inhibitory- and β subfamily.[full citation needed] The bactridines have many ...
Carterall, William A. (2001). "Molecular mechanisms of gating and drug block of sodium channels". Sodium Channels and Neuronal ... Blocking sodium channels in the conduction system, as well as the muscle cells of the heart, raises the depolarization ... MEGX has a longer half-life than lidocaine, but also is a less potent sodium channel blocker. The volume of distribution is 1.1 ... This means it works by blocking sodium channels and thus decreasing the rate of contractions of the heart. When injected near ...
Torsades de pointes
... this will result in increasing permeability of sodium channels, which trigger the opening of sodium channels. Repolarization of ... Phase 1: Sodium channels close; this stops depolarization. Potassium channels open, leading to an outward current of K+ out of ... This imbalance is corrected by the Na+/K+-ATPase channel that pumps K+ into the cell and sodium out of the cell; this does not ... Phase 2: Potassium channels remain open (outward current of K+), and calcium channels now also open (inward current of Ca++), ...
Kenneth B. Eisenthal
Araya, R.; Nikolenko, V.; Eisenthal, K. B.; Yuste, R. (2007). "Sodium channels amplify spine potentials". Proceedings of the ...
The cells lose sodium channels. The loss of the sodium channels is triggered by the opening of the eye correlating to the ... They lack protein channels for sodium and are more sensitive to certain neurotransmitters. They function by propagating graded ... Upon the opening of the eyes, these cells begin to shed their sodium ion channels and become non-spiking neurons. It was ... A calcium transporter study indicates the effect that protein channels have on the overall fidelity and firing capacity of the ...
Araya, R.; Nikolenko, V.; Eisenthal, K. B.; Yuste, R. (2007). "Sodium channels amplify spine potentials". PNAS. 104 (30): 12347 ... we now suspect that there are voltage-dependent sodium, potassium, and calcium channels in the spine heads. Cable theory ... "Local postsynaptic voltage-gated sodium channel activation in dendritic spines of olfactory bulb granule cells". Neuron. 85 (3 ... Ngo-Anh, T. J.; Bloodgood, B. L.; Lin, M.; Sabatini, B. L.; Maylie, J.; Adelman, J. P. (2005). "SK channels and NMDA receptors ...
... affects the gating mechanism of sodium channels by binding to neurotoxin receptor site 4 of the channel, resulting in ... Cestèle, S.; Catterall, W.A. (2000). "Molecular mechanisms of neurotoxin action on voltage-gated sodium channels". Biochimie. ... Due to the change in the activation the sodium channel will open at smaller depolarisations. This causes increased excitability ... Gordon, D.; Savarin, P.; Gurevitz, M.; Zinn-Justin, S. (1998). "Functional anatomy of scorpion toxins affecting sodium channels ...
It selectively blocks Acid Sensing Ion Channel 1-a (ASIC1a), which is a proton-gated sodium channel. Psalmotoxin is a toxin ... ASICs are proton-gated sodium channels. ASICs open when H+ binds. This occurs when the H+-concentration in the environment of ... Psalmotoxin can bind to a particular isoform of the Acid Sensing Ion Channel, the Acid Sensing Ion Channel 1 (ASIC1). The ... The channel being desensitized means that the ion channel is bound to its ligand, H+, but is not able to let ions pass through ...
In insects, DDT opens sodium ion channels in neurons, causing them to fire spontaneously, which leads to spasms and eventual ... Insects with certain mutations in their sodium channel gene are resistant to DDT and similar insecticides. DDT resistance is ... Dong, Ke (March 2007). "Insect sodium channels and insecticide resistance". Invertebrate Neuroscience : IN. 7 (1): 17-30. doi: ...
"BACE1 regulates voltage-gated sodium channels and neuronal activity". Nature Cell Biology. 9 (7): 755-764. doi:10.1038/ncb1602 ...
... is a sodium channel blocker. It binds preferentially to voltage-gated sodium channels in their inactive ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, ... and calcium channel blockers. Carbamazepine also increases the metabolism of the hormones in birth control pills and can ... "Sodium valproate versus phenytoin monotherapy for epilepsy: an individual participant data review". The Cochrane Database of ...
A recent study using X-ray crystallography showed that CBD binds inside the sodium channel pore at a novel site at the ... In vitro, cannabidiol inhibited the activity of voltage-dependent sodium and potassium channels, which may affect neural ... "Cannabidiol interactions with voltage-gated sodium channels". eLife. 9. doi:10.7554/eLife.58593. PMC 7641581. PMID 33089780. ... The pharmacological effects of CBD may involve PPARγ agonism, inhibition of voltage-gated cation channels, and intracellular ...
... -1 and -2 block A-type voltage-gated potassium channels; phrixotoxin-3 blocks voltage-gated sodium channels. Similar ... voltage-gated sodium channels by causing a depolarizing shift in gating kinetics and by blocking the inward component of sodium ... inhibits several voltage gated sodium channel subtypes (Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.4/SCN4A, Nav1.5/SCN5A, and Nav1.8/ ... "Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes". Mol Pharmacol. 69 (2): 419-29. ...
Neurotoxic shellfish poisoning
"Shellfish Toxins Targeting Voltage-Gated Sodium Channels". Marine Drugs. 11 (12): 4698-4723. doi:10.3390/md11124698. ISSN 1660- ... a group of greater than ten lipid-soluble cyclic polyethers that bind to a specific site on the voltage-gated sodium channel ( ... VGSC), leading to an influx of sodium ions into the cell. This results in activation of nerves and spontaneous nerve cell ...
Bioinspired Artificial Sodium and Potassium Ion Channels". In Astrid, Sigel; Helmut, Sigel; Roland K.O., Sigel (eds.). The ... Channel formers that introduce a hydrophilic pore into the membrane, allowing ions to pass through without coming into contact ... Channel forming ionophores are usually large proteins. This type of ionophores can maintain their ability to transfer ions at ... Examples of channel-forming ionophores are gramicidin A and nystatin. Ionophores that transport hydrogen ions (H+, i.e. protons ...
The drug also blocks atrial sodium channels. After infusion, the substance is rapidly distributed in the body. In the blood ... It differs from typical class III agents by blocking a certain type of potassium channel, the cardiac transient outward ... It also slightly blocks the hERG potassium channel, leading to a prolonged QT interval. This may theoretically increase the ... Like other class III antiarrhythmics, vernakalant blocks atrial potassium channels, thereby prolonging repolarization. ...
Bioinspired Artificial Sodium and Potassium Ion Channels". In Astrid S, Helmut S, Roland KO S (eds.). The Alkali Metal Ions: ... Plasmodesmata have been identified as functional channels interconnecting plant cells, and stromules interconnect plastids. ...
Hyperkalemic periodic paralysis
... this sodium leak raises the membrane potential to the point that all sodium channels, including channels produced from the wild ... Cannon, Stephen C. (2018). "Sodium Channelopathies of Skeletal Muscle". Voltage-gated Sodium Channels: Structure, Function and ... The mutation which causes this disorder is dominant on SCN4A with linkage to the sodium channel expressed in muscle. The ... This gene codes for a voltage-gated sodium channel Nav1.4 found at the neuromuscular junction. This condition is inherited in ...
The channels contain the sodium, Na, atoms. The unit cell parameters are a = 11 Å, b = 10 Å, c = 8.5 Å and β = 100°, with 4 ... Vlasovite is a rare inosilicate (chain silicate) mineral with sodium and zirconium, with the chemical formula Na2ZrSi4O11. It ... Peralkaline rocks are deficient in aluminium but have sodium and potassium in excess of the amount needed to form feldspar). At ... octahedra to form a framework with channels extending along , parallel to the c crystal axis. ...
Tetrodotoxin, a sodium channel antagonist, was found to prevent the sodium and calcium influxes caused by antillatoxin. Other ... Antillatoxin activates voltage-gated sodium channels, thus increasing sodium influx into the cell. It is hypothesized that ATX ... Antillatoxin is a sodium channel gating modifier with special efficacy in cells expressing rNav1.2, rNav1.4 and rNav1.5 α ... It is suggested that ATX preferentially binds to the voltage-gated sodium channel in the inactivated state. The specific site ...
... the fast-acting sodium and the inward-rectifying potassium. Though successful in predicting the timing and qualitative features ... Voltage sensitive ion channels are glycoprotein molecules which extend through the lipid bilayer, allowing ions to traverse ...
Other potassium channels like large conductance calcium-dependent potassium channels and sodium chloride dependent potassium ... NALCN sodium leak channels appear to give rise to an inward current that may play an important role in the modulation of ... Since NALCN sodium leak channels appear to contribute to the depolarization of neurons, their regulation by G-protein coupled ... These nonselective cation channels provide a voltage-independent sodium current that also helps slightly depolarize neurons. ...
Amphibian - Simple English Wikipedia, the free encyclopedia
Evolutionary diversification of TTX-resistant sodium channels in a predator-prey interaction. Nature 434: 759-763. ... They also move their tadpoles by using their nose to dig a channel to another place where there is more water.p9 They do ... Channel Islands slender salamander · Gabilan Mountains slender salamander · Garden slender salamander · Gregarious slender ...
ion channel activity. • benzodiazepine receptor activity. • chloride channel activity. • extracellular ligand-gated ion channel ... inhibitory extracellular ligand-gated ion channel activity. • GABA-gated chloride ion channel activity. • transmitter-gated ion ... chloride channel complex. • cell junction. • plasma membrane. • GABA-ergic synapse. • integral component of postsynaptic ... which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as ...
... which opens ion channels (largely sodium channels, though calcium can enter through these channels as well). The positive ... Thus, the random opening or closing of sodium channels will not affect the membrane potential of the cell; only the closing of ... as well as voltage-gated sodium channels. The membranous photoreceptor protein opsin contains a pigment molecule called retinal ... As a result, sodium ions can no longer enter the cell, and the photoreceptor outer segment membrane becomes hyperpolarized, due ...
Sodium salts of fatty acids are used as soap. Pure sodium metal also has many applications, including use in sodium-vapour ... Hellgren, Mikko; Sandberg, Lars; Edholm, Olle (2006). "A comparison between two prokaryotic potassium channels (KirBac1.1 and ... Lithium burns in air to form lithium oxide, but sodium reacts with oxygen to form a mixture of sodium oxide and sodium peroxide ... Sodium Magnesium Aluminium Silicon Phosphorus Sulfur Chlorine Argon Potassium Calcium Scandium Titanium Vanadium Chromium ...
Senarai reka cipta pada zaman pertengahan Islam Bahasa Melayu, ensiklopedia bebas
Ancient Discoveries]], Episode 12: Machines of the East, History Channel, dicapai 2008-09-08. Konflik URL-wikilink (bantuan) ... Sabun: Sabun sekarang digunakan dalam zaman moden diperbuat dari minyak sayur-sayuran (seperti minyal zaitun) dengan sodium ... Ancient Discoveries]], Episode 12: Machines of the East, History Channel, dicapai 2008-09-07. Konflik URL-wikilink (bantuan) ... Ancient Discoveries]], Episode 12: Machines of the East, History Channel, dicapai 2008-09-06. Konflik URL-wikilink (bantuan) ...
GABAA receptor positive allosteric modulator
But if the γ2 is expressed with α1 and β2 the sensitivity is low and channel conductance is high. γ2 subunit has to be ... Bromide compounds (e.g., lithium bromide, potassium bromide, sodium bromide). *Carbamazepine. *Chloralose ... Upon binding, it triggers the GABAA receptor to open its chloride channel to allow chloride ions into the neuron, making the ... The channel conductance is not higher in the presence of benzodiazepine and GABA than the conductance with the presence of only ...
"Mitochondrial Ion Channels: Gatekeepers of Life and Death". Physiology. 20 (5): 303-315. doi:10.1152/physiol.00020.2005. ISSN ...
腎上腺素 - 維基百科，自由的百科全書
鈉離子通道阻滯劑（英語：Sodium channel blocker） (SCB) ... 鉀離子通道阻滯劑（英語：Potassium channel blocker） (PCB) ... 鉀離子通道開放劑（
In January 2018, YouTube deleted Nitschke's YouTube channel "Exityourtube". The channel had been operating for 10 years. ... October 2009 Nitschke announced his intention to inform people at his workshops where to obtain a long-storage form of sodium ... The program aired in October in China on the Family Health channel, run by the official China National Radio. ... The program aired in October in China on the Family Health channel, run by the official China National Radio. ...
This opens stretch-sensitive ion channels of the sensory endings, leading to an influx of sodium ions. This raises the resting ... These fibres send information by stretch-sensitive mechanically-gated ion-channels of the axons. ...
States in which ginger is exported follow the marketing channels of vegetable marketing in India, and the steps are similar to ... water channels are made 60-80 ft apart to irrigate the crop. ... See also: Receptor/signaling modulators • Ion channel ...
藥物過量 - 维基百科，自由的百科全书
Calcium Channel Blockers. CCB. 降血壓. 鈣質. Calcium. -. 骨骼細胞營養所需 ... Sodium Bicarbonate. 小蘇打（Baking soda）. 食物添加劑 ... Better Health Channel. [2011-07-21]. （原始内
Kao CY and Levinson SR (1986) Tetrodotoxin, saxitoxin, and the molecular biology of the sodium channel New York Academy of ... Saxitoxin has been used in molecular biology to establish the function of the sodium channel. It acts on the voltage-gated ... The blocking of neuronal sodium channels which occurs in paralytic shellfish poisoning produces a flaccid paralysis that leaves ... sodium channels of nerve cells, preventing normal cellular function and leading to paralysis. ...
calcium channel activity. • metal ion binding. • voltage-gated ion channel activity. • ion channel activity. • protein binding ... voltage-gated calcium channel activity involved in cardiac muscle cell action potential. • high voltage-gated calcium channel ... When calcium ions bind to calmodulin, which in turn binds to a Cav1.2 channel, it allows the Cav1.2 channels within a cluster ... This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ...
Peluh Bahasa Melayu, ensiklopedia bebas
Hanukoglu I, Boggula VR, Vaknine H, Sharma S, Kleyman T, Hanukoglu A (January 2017). "Expression of epithelial sodium channel ( ...
Epithelial sodium channel blockers: amiloride and triamterene.. Calcium-sparing diureticsEdit. The term "calcium-sparing ... Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels. ... Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. ... This is large in comparison to normal renal sodium reabsorption which leaves only about 0.4% of filtered sodium in the urine. ...
Acute inhalation injury
Others modulate the activity of ion channels that control fluid transport across lung membranes or target surfactant, a ... sodium sulphide) in an ovine model of burn- and smoke-induced acute lung injury. Br J Pharmacol. 158:1442-53.. ... Inhibition of lung fluid clearance and epithelial Na+ channels by chlorine, hypochlorous acid, and chloramines. J Biol Chem. ...
Some "triple-action" pepper sprays also contain "tear gas" (CS gas), which can be neutralized with sodium metabisulfite ( ... See also: Receptor/signaling modulators • Ion channel modulators. Retrieved from "https://en.wikipedia.org/w/index.php?title= ...
Brain-derived neurotrophic factor
While AMPA receptor activation leads to depolarization via sodium influx, NMDA receptor activation by rapid successive firing ... will communicate regularly and maintain the synapse structure and function long after the initial activation of NMDA channels. ... allows calcium influx in addition to sodium. The calcium influx triggered through NMDA receptors can lead to expression of BDNF ...
Times Beach, Missouri
"Engineering Disasters" Modern Marvels, History Channel, Viewed March 4, 2010 *^ a b c d e f g h i j k l m Hernan, Robert (2010 ... 5-tetrachlorobenzene by the nucleophilic aromatic substitution reaction with sodium hydroxide (NaOH). Unfortunately, ... The story of Times Beach was featured on History Channel's Modern Marvels, in the episode "Engineering Disasters 20". ...
The most common form uses methanol (converted to sodium methoxide) to produce methyl esters (commonly referred to as Fatty Acid ... The hand-sized square piece of metal contains microscopic channels with catalytic sites, which continuously convert biodiesel, ... While studying the effect of biodiesel on diesel particulate filters, it was found that though the presence of sodium and ...
This can give rise to elevated concentrations of sodium, chloride, magnesium and sulfate as well as many other compounds in ... which underlies many larger rivers and can contain substantially more water than is seen in the open channel. It may also be in ...
Ion channel. modulators. Calcium blockers. *Gabapentin. *Gabapentin enacarbil. *Mirogabalin. *Pregabalin. *Ziconotide. Sodium ...
Rough-skinned newt - Simple English Wikipedia, the free encyclopedia
Evolutionary diversification of TTX-resistant sodium channels in a predator-prey interaction. Nature 434: 759-763. ...
Reconstitution with sodium chloride should be avoided due to formation of precipitates. Intravenous solutions of pentamidine ... L-Type calcium channel blockers (e.g., dihydropyridines: nifedipine). *Nebivolol (beta blocker) ...
... or epithelial sodium channel blockers such as amiloride can be used to decrease urinary wasting of potassium. ... This symporter is a channel responsible for the transport of multiple electrolytes such as sodium, chloride, calcium, magnesium ... channel (ClC-Kb), and the Na+/K+-ATPase. Indicated also are the recently identified magnesium channel TRPM6 in the apical ... Sodium chloride (NaCl) enters the cell via the apical thiazide-sensitive NCC and leaves the cell through the basolateral Cl− ...
Varying amounts of potassium, sodium, phosphorus, calcium, magnesium, iron, and zinc were present. ... Visual neuron of the locust, Ri Channel video, October 2011. *FAO Locust Watch ...
Mold health issues
... due to absorption into cells and production of nano-channels that obstruct vital ion channels that ferry potassium and sodium ... and 11-residue peptaibols from the fungus Trichoderma longibrachiatum are synergistic in forming Na+/K+-permeable channels and ...
Sodium channel blocker - Wikipedia
Sodium channel blockers are drugs which impair the conduction of sodium ions (Na+) through sodium channels. ... Sodium channel opener. References. *^ Sodium+Channel+Blockers at the US National Library of Medicine Medical Subject ... sodium channels.. Antiarrhythmic. Sodium channel blockers are used in the treatment of cardiac arrhythmia. They are ... Drugs which block sodium channels by blocking from the intracellular side of the channel include: *Local anesthetics: lidocaine ...
Sodium channels in cardiac Purkinje cells | SpringerLink
Sodium (Na+) currents are responsible for excitation and conduction in most cardiac cells, but their study has been hampered by ... Bean, B. P., Cohen, C. J., and Tsien, R. W., Block of cardiac sodium channels by tetrodotoxin and lidocaine: Sodium currents ... Aldrich, R. W., Corey, D. P., and Stevens, C. F., A reinterpretation of mammalian sodium channel gating based on single channel ... Colatsky, T. J., and Tsien, R. W., Sodium channels in rabbit cardiac Purkinje fibres. Nature278 (1979) 265-268.PubMedGoogle ...
Epithelial sodium channel (IPR001873) | InterPro | EMBL-EBI
The apical membrane of many tight epithelia contains sodium channels that are primarily characterised by their high affinity to ... Membrane topology of the amiloride-sensitive epithelial sodium channel.. J. Biol. Chem. 269 24379-83 1994 ... Membrane topology of the amiloride-sensitive epithelial sodium channel.. J. Biol. Chem. 269 24379-83 1994 ... the channels control reabsorption of sodium in kidney, colon, lung and sweat glands; they also play a role in taste perception. ...
Structure of sodium channels different than previously believed | EurekAlert! Science News
New Cambridge research provides fresh and unexpected insight into the structure of sodium channels and, specifically, one of ... Sodium channels are implicated in many serious conditions such as heart disease, epilepsy and pain, making them an important ... its components -- β-subunit molecules -- which are responsible for fine-tuning the activity of the channel. The research is ... and sodium channels play a vital role in this process. The sodium channel lies on the surface of the nerve and muscle cells and ...
Species: Epithelial sodium channel (IPR001873) | InterPro | EMBL-EBI
Prostasin: An Epithelial Sodium Channel Regulator
"Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease ... Prostasin: An Epithelial Sodium Channel Regulator. Shakti Aggarwal,1 Pradeep K. Dabla,2 and Sarika Arora1 ... S. H. Donaldson and R. C. Boucher, "Sodium channels and cystic fibrosis," Chest, vol. 132, no. 5, pp. 1631-1636, 2007. View at ... J. M. Hollier, D. F. Martin, D. M. Bell et al., "Epithelial sodium channel allele T594M is not associated with blood pressure ...
A melanosomal two-pore sodium channel regulates pigmentation | Scientific Reports
Here we identify two-pore channel 2 (TPC2) as the first reported melanosomal cation conductance by directly patch-clamping skin ... How to cite this article: Bellono, N. W. et al. A melanosomal two-pore sodium channel regulates pigmentation. Sci. Rep. 6, ... Bellono, N., Escobar, I. & Oancea, E. A melanosomal two-pore sodium channel regulates pigmentation. Sci Rep 6, 26570 (2016). ... A melanosomal two-pore sodium channel regulates pigmentation. *Nicholas W. Bellono1 na1 nAff2, ...
Sodium Channels in refractory period | Physics Forums
Related Threads on Sodium Channels in refractory period Refractory Period for Neurone ... Therefore, there is no reason why sodium channels should not be able to open due to that reason. ... Therefore, there is no reason why sodium channels should not be able to open due to that reason. ... Therefore, there is no reason why sodium channels should not be able to open due to that reason. ...
BACE Regulates Sodium Channels, Neuronal Excitability | ALZFORUM
Voltage-gated sodium channels are composed of a pore-forming α subunit, and one or two regulatory β subunits. Researchers knew ... The end result, a loss of functional channels at the cell membrane, reduces sodium currents in the cells and thus affects ... BACE1 regulates voltage-gated sodium channels and neuronal activity. Nat Cell Biol. 2007 Jul;9(7):755-64. PubMed. ... What of the functional ramifications of β2 cleavage? The researchers looked at sodium channel function by whole-cell voltage- ...
Amiloride-Sensitive Sodium Channels: Physiology and Functional Diversity, Volume 47 - 1st Edition
Purchase Amiloride-Sensitive Sodium Channels: Physiology and Functional Diversity, Volume 47 - 1st Edition. Print Book & E-Book ... P.R. Smith, cAMP Mediated Regulation of Amiloride-Sensitive Sodium Channels: Channel Activation or Channel Recruitment?. J.K. ... entry through an amiloride-sensitive sodium channel and exit via the ouabain-sensitive sodium/potassium ATPase. The sodium ... Subunit Stoichiometry of Heteroligomeric and Homoligomeric Epithelial Sodium Channels.. Regulation of Sodium Channels:. N. ...
Sodium channel selectivity filter regulates antiarrhythmic drug binding | PNAS
The Shaker K+ channel is thought to have a pore structure analogous to that of the Na+ channel. In the brain IIA Na+ channel, ... The Selectivity Filter of the Voltage-gated Sodium Channel Is Involved in Channel Activation ... The Selectivity Filter of the Voltage-gated Sodium Channel Is Involved in Channel Activation ... channels by interacting with two parts of the K+ channel inner pore, the P loop near the channels selectivity filter and the ...
Evolution of sodium channels predates the origin of nervous systems in animals | PNAS
Voltage-dependent sodium channels are believed to have evolved from calcium channels at the origin of the nervous system. A ... Sodium channels also have a cytoplasmic loop between their third and fourth domains that swings up and occludes the channel ... 1992) Calcium channel characteristics conferred on the sodium channel by single mutations. Nature 356:441-443. ... 2) and have key molecular signatures of sodium channels (Fig. 3). Others have proposed that Nav channels evolved from an ...
Potassium, sodium, calcium and glutamate-gated channels: pore architecture and ligand action. - PubMed - NCBI
Potassium, sodium, calcium and glutamate-gated channels: pore architecture and ligand action.. Zhorov BS1, Tikhonov DB. ... residues are conserved in P-loop channels that include high-selective cation channels and certain ligand-gated channels. X-ray ... Data on binding sites and mechanisms of action of ligands of K+, Na+, Ca2+ and glutamate gated ion channels are considered in ... In the last decade, the idea of common organization of certain ion channel families exhibiting diverse physiological and ...
The crystal structure of a voltage-gated sodium channel. - PubMed - NCBI
Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs ... The crystal structure of a voltage-gated sodium channel.. Payandeh J1, Scheuer T, Zheng N, Catterall WA. ... Voltage-gated sodium channels - overview and references - Guide to Pharmacology. Miscellaneous. *CALCIUM, ELEMENTAL - Hazardous ... a, Pore-lining S6 helices of NavAb (yellow) and the closed MlotiK (3BEH), KcsA (1K4C) and NaK (2AHY) channels. Cα locations of ...
Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel
Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers
Sodium channel blockers. The firing of an action potential by an axon is accomplished through sodium channels. Each sodium ... Sodium Channel Blockers. Sodium channel blockade is the most common and best-characterized mechanism of currently available ... The NMDA site opens a channel that allows large amounts of calcium to enter along with the sodium ions. This channel is blocked ... AEDs that target the sodium channels prevent the return of these channels to the active state by stabilizing them in the ...
... conducting sodium ions (Na+) through a cells plasma membrane. They may ... Sodium channel Sodium channels are integral membrane proteins that form ion channels, ... Na+: Sodium channel. Navα (1.1, 1.2, 1.4, 1.5, 1.7, 1.9) • Navβ (1, 3, 4) • Epithelial sodium channel. ... voltage-gated sodium channels) or binding of a substance (a ligand) to the channel (ligand-gated sodium channels). ...
Sodium Channel News, Articles | The Scientist Magazine®
sodium channel. Genetic Mutation Linked to Cot Death. Catherine Offord , Mar 29, 2018. Alterations to a protein involved in ... Targeting Sodium Channels for Pain Relief. Catherine Offord , Dec 31, 2017. The race to develop analgesic drugs that inhibit ... Since the mid-2000s, the voltage-gated sodium channel NaV1.7 has emerged as a promising target for a new class of analgesics. ... Grasshopper mice harbor mutations in a pain-transmitting sodium channel that allow them to prey on highly toxic bark scorpions. ...
Targeting Neuroglial Sodium Channels in Neuroinflammatory Diseases | IntechOpen
As the core player of AP initiation, voltage-gated sodium channels (VGSCs) are always considered to be required for ... 4. Neuroglial sodium channels in neurodegenerative diseases. 4.1 Neuroglial sodium channels in Alzheimers disease. AD is the ... a TTX-resistant sodium channel) . The blockade sodium channels of TTX and phenytoin could significantly weaken a variety of ... including the TTX-S sodium channel Nav1.3 and Nav1.6 as well as TTX-R sodium channel Nav1.5 . In the post-status ...
JCI - Inactivation of sodium channels underlies reversible neuropathy during critical illness in rats
Both resting potential and voltage dependence of sodium channel inactivation determine the percentage of sodium channels ... of sodium channels are available. The difference in percentage of sodium channels available leads to a small action potential ... the voltage dependence of sodium channel inactivation is positioned such that only a minority of sodium channels are ... One way that voltage dependence of sodium current might be shifted is a change in sodium channel isoform expression (37, 38). ...
Interactions between Stavzor Oral and sodium-channel-blocker-potassium-channel-blocker-lacosamide
JCI - Sodium channel mutations in epilepsy and other neurological disorders
Since the first mutations of the neuronal sodium channel SCN1A were identified 5 years ago, more than 150 mutations have been ... The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological ... Mutations resulting in persistent sodium current are also common. Coding variants of SCN2A, SCN8A, and SCN9A have also been ...
A One-Domain Voltage-Gated Sodium Channel in Bacteria | Science
Voltage-gated sodium channels are a feature of excitable mammalian cells such as neurons, but have never been found in bacteria ... In his Perspective, Catterall discusses the discovery of the first bacterial voltage-gated sodium channel ( Ren et al.) and ... compares the structure and function of this channel with its mammalian counterpart. ...
Crystal structure of a voltage-gated sodium channel in two potentially inactivated states | Nature
There are many published structures for potassium channels, but structural information on voltage-gated sodium (Nav) channels ... In excitable cells, voltage-gated sodium (NaV) channels activate to initiate action potentials and then undergo fast and slow ... Bacterial Nav channels provide a good model system for structure-function analyses, and here two groups report the X-ray ... Compared to previous structures of NaVAb channels with cysteine mutations in the pore-lining S6 helices (ref. 4), the S6 ...
Frontiers | Propranolol Blocks Cardiac and Neuronal Voltage-Gated Sodium Channels | Pharmacology
Heterologous Expression of Sodium Channels. A recombinant human NaV1.5 sodium channel cDNA in a mammalian expression plasmid ( ... We established that cardiac sodium channels have greater affinity for propranolol than brain sodium channels, that block is not ... These data indicate that brain sodium channels exhibit less sensitivity to R-(+)-propranolol than NaV1.5 channels. Based upon ... Finally, we observed that brain sodium channels exhibited less sensitivity to R-(+)-propranolol than NaV1.5 channels. Our ...
What Is a Sodium Channel Blocker? (with pictures)
A sodium channel blocker is a medication that is used to correct abnormal heart rhythms by affecting the electrical impulses ... A sodium channel blocker is a medication that is categorized as a Class I antiarrhythmic drug. This means that it works to ... Typically, a sodium channel blocker may cause dizziness, nausea, and vomiting, along with diarrhea or constipation. Loss of ... People taking a sodium channel blocker may experience some side effects, which should be reported to the prescribing physician ...
Search of: 'Status Epilepticus' | 'Sodium Channel Blockers' - List Results - ClinicalTrials.gov
Search of: LIDOCAINE AND Sodium Channel - Results on Map - ClinicalTrials.gov
Hints: Click on a [map] link to show a map of that region. Click on a [studies] link to search within your current results for studies in that region. Use the back button to return to this list and try another region. Studies with no locations are not included in the counts or on the map. Studies with multiple locations are included in each region containing locations ...
Functional Analysis of the Mouse Scn8a Sodium Channel | Journal of Neuroscience
Diagram of the Scn8a sodium channel.A, Diagram of the Scn8a sodium channel, showing the differences between the sequence of the ... properties of Scn8a sodium channels were very similar to those of Rat1 and Rat2 sodium channels when all three channels were ... 1997) Persistent sodium currents through brain sodium channels induced by G-protein βγ subunits. Neuron 19:443-452. ... 1998) The sodium channel Scn8a is the major contributor to the postnatal developmental increase of sodium current density in ...
RCSB PDB - 2ITC: Potassium Channel KcsA-Fab complex in Sodium Chloride
Potassium Channel KcsA-Fab complex in Sodium Chloride. *DOI: 10.2210/pdb2ITC/pdb ... Channels: Potassium, Sodium, & Proton Ion-Selective. Protein: KcsA-Fab complex in NaCl. ... Voltage-gated potassium channel. C. 124. Streptomyces lividans. Mutation(s): 1 Gene Names: kcsA, skc1. ... Structural and Thermodynamic Properties of Selective Ion Binding in a K(+) Channel.. Lockless, S.W., Zhou, M., Mackinnon, R.. ( ...
Epithelial Sodium ChannelsIonsNeuronsENaCCurrentsExcitableMutationsBlockerProteinBlockersProteinsPharmacologyAlpha subunitMolecularIsoformsGenesGeneRegulationPharmacologicalPotassiumCalciumMembraneAmiloride SensitivMutationSubunitPoreInhibitConductanceInactivation of the sodiumMechanismsInhibitionMechanismInhibitorContain sodiumAntibodyVoltageSCN8AMammalian sodiumModulationExpressionSelectivity filterSelectivelyVariantsLidocaineApicalInteractionsBlock sodium channelsNav1.7Shown to modulate
Epithelial Sodium Channels7
- The epithelial sodium channels are structurally and probably evolutionary related to P2X purinoreceptors, pain receptors that activate when they detect ATP. (wikipedia.org)
- Epithelial sodium channels facilitate Na⁺ reabsorption across the apical membranes of epithelia in the distal nephron, respiratory and reproductive tracts and exocrine glands. (wikipedia.org)
- Cytokines and chemokines affect alveolar amiloride-sensitive epithelial sodium channels (ENaCs), which play a crucial role in sodium transport and fluid reabsorption in the lung. (frontiersin.org)
- Of the renal sodium transporters, the amiloride-sensitive epithelial sodium channels (ENaC), which are responsible for the rate-limiting step of sodium reabsorption in the distal nephron, are therefore important candidates in the development of hypertension. (aspetjournals.org)
- Degenerin/epithelial sodium channels (DEG/ENaC) represent a large family of animal-specific membrane proteins. (pubmedcentralcanada.ca)
- One of the best known potassium sparing diuretics - amiloride - blocks the action of so-called epithelial sodium channels (ENaCs), which have diverse physiological functions. (phys.org)
- Controlling epithelial sodium channels with light using photoswitchable amilorides. (phys.org)
- Sodium channel blockers are drugs which impair the conduction of sodium ions (Na + ) through sodium channels . (wikipedia.org)
- The way it accomplishes the depolarization is via the influx of sodium ions across the cell membrane facilitated by ion channels specific to sodium. (physicsforums.com)
- This repositioning of ions, again accomplished by channels takes time and therefore accounts for the period during which further signals cannot be sent. (physicsforums.com)
- They are the fuel and ions channels are a kind of engines that work with ions. (physicsforums.com)
- You are correct that in the cell as a whole there are enough ions, but these events happen in very localized environments surrounding those channels. (physicsforums.com)
- So am I correct in saying that the absolute refractory period is due to the lack of ions in the localised environments not because of the inability of the protein channels to open immediately after they are closed? (physicsforums.com)
- Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions ( Na + ) through a cell's plasma membrane . (bionity.com)
- They may be classified according to the trigger that opens the channel the such ions, i.e. either a voltage-change (voltage-gated sodium channels) or binding of a substance (a ligand) to the channel (ligand-gated sodium channels). (bionity.com)
- When stimulated by a change in transmembrane voltage , this region moves toward the extracellular side of the cell membrane, allowing the channel to become permeable to ions. (bionity.com)
- Each of these variables can attain a value between 1 (fully permeant to ions) and 0 (fully non-permeant), the product of these variables yielding the percentage of conducting channels. (bionity.com)
- The pore of sodium channels contains a selectivity filter made of negatively charged amino acid residues, which attract the positive Na + ion and keep out negatively charged ions such as chloride . (bionity.com)
- The epithelial sodium channel (short: ENaC, also: amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to the ions of sodium (Na+ ) and that is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. (wikipedia.org)
- It is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. (wikipedia.org)
- Sodium channels (also known as "voltage-gated sodium channels") are integral membrane proteins that conduct sodium ions ( Na + ) through a cell's plasma membrane . (wikidoc.org)
- Many of the ionotropic receptors are also able to conduct sodium ions. (wikidoc.org)
- Normally, the Nav channels open in response to a change in electrical potential, allowing sodium ions to enter the cell, but then the channels inactivate quickly, usually in a few milliseconds. (albany.edu)
- Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na + ions may pass in accordance with their electrochemical gradient. (uniprot.org)
- Around 1000 sodium ions pass in the next millisecond , before the channel spontaneously closes (an event with single step kinetics ). (biology-online.org)
- A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. (semanticscholar.org)
- ENaCs are heterotrimeric proteins that form channels in the cell membrane and allow the passage of sodium ions (Na+). (phys.org)
- Turning off the light or irradiating the cells with green light alters the shape of the compound in such a way that the block is released and sodium ions flow through the channel pore into the cell. (phys.org)
- There has been much speculation that aberrant influx of sodium ions through ENaCs might contribute to the pathogenesis of neuronal diseases by causing persistent, uncontrolled firing by nerve cells. (phys.org)
- In addition, our photoamiloride/ENaC system can be used to manipulate the polarization state of cells - the magnitude of the electrical potential across the cell membrane - by altering the flow of sodium ions through these channels," Dirk Trauner adds. (phys.org)
- Sodium channels conduct Na+ ions into cells, thereby initiating electrical signals that drive thoughts and heart beats. (jhu.edu)
- These cells can generate far stronger electrical impulses than those of normal nerve or muscle cells, but the impulses are initiated in the same way, by the flow of sodium ions into the cell through voltage-gated sodium channels. (wordpress.com)
- In a new paper, Dora Kovacs and colleagues at Harvard Medical School reveal a role for BACE in regulating the expression of voltage-gated sodium channels in neurons. (alzforum.org)
- Rapid, specific, long-distance communication among excitable cells is achieved in bilaterian animals and a few jellyfish (cnidarians) through the use of action potentials (APs) in neurons generated by voltage-dependent sodium (Na v ) channels. (pnas.org)
- Many structures and processes are involved in the development of a seizure, including neurons, ion channels, receptors, glia, and inhibitory and excitatory synapses. (medscape.com)
- In excitable cells such as neurons and myocytes , sodium channels are responsible for the rising phase of action potentials . (bionity.com)
- Voltage-gated sodium channels are a feature of excitable mammalian cells such as neurons, but have never been found in bacteria. (sciencemag.org)
- The unique persistent current observed for Scn8a channels is consistent with the hypothesis that this channel is responsible for distinct sodium conductances underlying repetitive firing of action potentials in Purkinje neurons. (jneurosci.org)
- Although the physiological basis of erythermalgia, an autosomal dominant painful neuropathy characterized by redness of the skin and intermittent burning sensation of extremities, is not known, two mutations of Na v 1.7, a sodium channel that produces a tetrodotoxin-sensitive, fast-inactivating current that is preferentially expressed in dorsal root ganglia (DRG) and sympathetic ganglia neurons, have recently been identified in patients with primary erythermalgia. (jneurosci.org)
- These observations provide the first demonstration of altered sodium channel function associated with an inherited painful neuropathy and suggest that these physiological changes, which confer hyperexcitability on peripheral sensory and sympathetic neurons, contribute to symptom production in hereditary erythermalgia. (jneurosci.org)
- By using an extract prepared from cultured neocortical neurons, we demonstrated a biochemical interaction between mSlo2 channels and PSD-95, and a mutational analysis revealed that mSlo2 channels bound to the first PDZ domain of PSD-95 via the PDZ binding motif. (nih.gov)
- To investigate the expression of mSlo2 protein in primary neocortical neurons, we raised anti-mSlo2 channel antibody and immunostained neocortical neurons. (nih.gov)
- The immunocytochemical study showed that mSlo2 channels partly colocalized with PSD-95 in mouse neocortical neurons. (nih.gov)
- Bant JS, Raman IM (2010) Control of transient, resurgent, and persistent current by open-channel block by Na channel beta4 in cultured cerebellar granule neurons. (springer.com)
- Nadeau H, Lester H. NRSF causes cAMP-sensitive suppression of sodium current in cultured hippocampal neurons. (labome.org)
- Voltage-gated sodium channels play an essential biophysical role in many excitable cells such as neurons. (eurekaselect.com)
- Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via [alpha]2-Adrenoceptors in Trigeminal Ganglion Neurons. (thefreelibrary.com)
- Voltage-gated sodium channels (VGSCs) play an important role in action potential initiation and propagation in excitable cells, including sensory neurons in the TG and DRG, because they are responsible for the initial depolarization of the membrane. (thefreelibrary.com)
- Recent studies have revealed that dexmedetomidine inhibits both tetrodotoxin-resistant and tetrodotoxin-sensitive sodium channels in DRG neurons [8,19, 20]. (thefreelibrary.com)
- The human Nav1.7 gene encodes the pore-forming subunit of a voltage-gated Na+ channel that is expressed in sensory and sympathetic neurons. (criver.com)
- We tested this by measuring the effect of the sodium channel blocker tetrodotoxin (TTX) on depolarizations generated by two-photon uncaging of glutamate on spines from mouse neocortical pyramidal neurons. (columbia.edu)
- Our data confirm that spines from neocortical pyramidal neurons are electrically isolated from the dendrite and indicate that they have sodium channels and are therefore excitable structures. (columbia.edu)
- Dorsal root ganglion neurons express an array of sodium channel isoforms allowing precise control of excitability. (ovid.com)
- The pattern of expression of sodium channels differs in different subclasses of DRG neurons and is not fixed but, on the contrary, changes in response to a variety of disease insults. (ovid.com)
- Moreover, modulation of channels by their environment has been found to play an important role in the response of these neurons to stimuli. (ovid.com)
- In this review we illustrate how excitability can be finely tuned to provide contrasting firing templates in different subclasses of DRG neurons by selective deployment of various sodium channel isoforms, by plasticity of expression of these proteins, and by interactions of these sodium channel isoforms with each other and with other modulatory molecules. (ovid.com)
- The discovery of the tetrodotoxin-resistant (TTX-R) Na + channel in nociceptive neurons has provided a special target for analgesic intervention. (dovepress.com)
- Over this same period we have recognized that mutations in such ion channels (many of which are selectively expressed in sensory neurons) can result in inherited pain disorders in humans. (mcgill.ca)
- Ion channels generate the electrical impulses produced by neurons and muscle cells, so their insertion into the membrane, and removal from it, is one way of modulating the electrical properties of the cells. (wordpress.com)
- Members of the epithelial Na + channel (ENaC) family fall into four subfamilies, termed alpha, beta, gamma and delta [ PMID: 8905643 ]. (ebi.ac.uk)
- In most ENaC proteins studied to date, the extracellular domains are highly conserved and contain numerous cysteine residues, with flanking C-terminal amphipathic TM regions, postulated to contribute to the formation of the hydrophilic pores of the oligomeric channel protein complexes. (ebi.ac.uk)
- Phylogenetic characterization of the epithelial Na+ channel (ENaC) family. (ebi.ac.uk)
- M. Driscoll, H.A. Thieringer, S. Sahota, and I. Mano , C. elegans Members of the DEG/EnaC Channel Superfamily: Form and Function. (elsevier.com)
- The epithelial Na + transport is generally mediated through two steps: (1) the entry step of Na + via epithelial Na + channel (ENaC) at the apical membrane and (2) the extrusion step of Na + via the Na + , K + -ATPase at the basolateral membrane. (hindawi.com)
- ENaC channels in the brain are involved in blood pressure response to dietary sodium. (wikipedia.org)
- In rodents, virtually the entire salt taste is mediated by ENaC, whereas it seems to play a less significant role in humans: About 20 percent can be accredited to the epithelial sodium channel. (wikipedia.org)
- Examples include toxins, such as aconitine, batrachotoxin, robustoxin, palytoxin and ciguatoxins and insecticides (DDT and pyrethroids), which activate voltage-gated sodium channels (VGSCs), and solnatide (AP301), which activates the epithelial sodium channel (ENaC). (wikipedia.org)
- The epithelial sodium channel (ENaC) is critical in the maintenance of the epithelial fluid layer. (frontiersin.org)
- The human SCNN1A, B and G genes encode the heteromeric ENaC channel, a constitutively active, amiloride-sensitive Na+-selective ion channel. (criver.com)
- Studying the polymorphic variants in the various subunits of ENaC may further our understanding of the mechanisms that underlie sodium balance in mammals. (aspetjournals.org)
- In this chapter, we will review the contribution of PCR-directed mutagenesis in the determination of the structure-function relationship of the epithelial sodium channel (ENaC), particularly with respect to the domains involved in proteolytic activation and ligand-induced stimulation of the channel. (intechopen.com)
- ENaC is a key component of the transepithelial sodium transport. (intechopen.com)
- ENaC is a heteromeric channel made of three subunits (α, β and γ) encoded by 3 different genes SCNN1a, SCNN1b and SCNN1g, respectively. (intechopen.com)
- One enigmatic group of ion channels is the Degenerin/epithelial Na + channel (DEG/ENaC) family. (pubmedcentralcanada.ca)
- Together, these data indicate that DEG/ENaC channels have evolved to serve many different physiological functions, acting as ionotropic receptors to diverse extracellular stimuli. (pubmedcentralcanada.ca)
- BOSTON and DURHAM, N.C., June 04, 2015 (GLOBE NEWSWIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) and Parion Sciences today announced that the companies will collaborate to develop investigational epithelial sodium channel (ENaC) inhibitors for the potential treatment of cystic fibrosis (CF) and other pulmonary diseases. (cnbc.com)
- Cannabidiol has been shown to cause inhibitory effects on sodium currents. (wikipedia.org)
- The current literature suggests that cannabidiol inhibits sodium currents primarily through altering the biophysical properties of cell membrane, promoting the inactivated conformation of * sodium channels . (wikipedia.org)
- Sodium (Na + ) currents are responsible for excitation and conduction in most cardiac cells, but their study has been hampered by the lack of a satisfactory method for voltage clamp. (springer.com)
- The end result, a loss of functional channels at the cell membrane, reduces sodium currents in the cells and thus affects membrane excitability. (alzforum.org)
- Among BACE-expressing cells, 65 percent totally lost sodium currents, while the rest had decreased average current density. (alzforum.org)
- The investigators obtained similar results with hippocampal slices from BACE1 mice, which displayed decreased sodium currents. (alzforum.org)
- This view was reinforced by the apparent lack of sodium currents in sponges ( 4 ). (pnas.org)
- Catterall, W. A. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. (nature.com)
- In contrast to dysregulated sodium channel expression, to date there have been no demonstrations of changes in sodium currents attributable to mutations associated with pain. (jneurosci.org)
- The diseased channels' persistent late currents are generally small in size (less than 2% of the peak current amplitude), making these channels difficult to study or use in the screening of new drug candidates. (albany.edu)
- To solve these problems, researchers at the University at Albany have generated and characterized a panel of modified Nav channels which open persistently like their diseased counterparts, but have considerably larger late sodium currents. (albany.edu)
- In drug screening, our inactivation-deficient Nav channels more closely mimic diseased channels than do wild-type channels, but have larger persistent currents, making therapeutic effects more detectable. (albany.edu)
- The two-electrode voltage clamp technique was used to measure sodium currents from unfertilized Xenopus frog eggs injected with rat Nav1.4 sodium channel and auxiliary [beta]1-subunit cRNA. (cornell.edu)
- One of the putative underlying mechanisms is impaired inactivation of voltage-gated sodium channels (VGSC), resulting in small persistent sodium currents. (queensu.ca)
- Nerves and other electrically-excitable cells communicate with one another by transmitting electrical signals, and sodium channels play a vital role in this process. (eurekalert.org)
- Voltage-gated sodium (Na(V)) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. (nih.gov)
- As the core player of AP initiation, voltage-gated sodium channels (VGSCs) are always considered to be required for electrogenesis in excitable cells. (intechopen.com)
- In excitable cells, voltage-gated sodium (Na V ) channels activate to initiate action potentials and then undergo fast and slow inactivation processes that terminate their ionic conductance 1 , 2 . (nature.com)
- Voltage-gated sodium channels play a critical role in the generation of action potentials in excitable cells throughout the nervous system ( Catterall, 1992 ). (jneurosci.org)
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. (uniprot.org)
- Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. (ovid.com)
- The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells. (semanticscholar.org)
- This fast inactivation makes sodium signaling reliable on the millisecond time scale, and mutations at this region in human Na v channel genes cause many well-known pathologies ( 19 ). (pnas.org)
- Grasshopper mice harbor mutations in a pain-transmitting sodium channel that allow them to prey on highly toxic bark scorpions. (the-scientist.com)
- Since the first mutations of the neuronal sodium channel SCN1A were identified 5 years ago, more than 150 mutations have been described in patients with epilepsy. (jci.org)
- Mutations resulting in persistent sodium current are also common. (jci.org)
- The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well. (jci.org)
- Compared to previous structures of Na V Ab channels with cysteine mutations in the pore-lining S6 helices (ref. 4 ), the S6 helices and the intracellular activation gate have undergone significant rearrangements: one pair of S6 helices has collapsed towards the central pore axis and the other S6 pair has moved outward to produce a striking dimer-of-dimers configuration. (nature.com)
- Nine off-site mutations in the paralogs sodium channel genes Scn5a and Scn4a were identified. (nih.gov)
- Both mutations cause a significant hyperpolarizing shift in the V 1/2 of activation of the mutant channel, which was accompanied by a larger ramp current. (jneurosci.org)
- This work identifies SCN8A as the fifth sodium channel gene to be mutated in epilepsy and demonstrates the value of [whole-genome sequencing] for the identification of pathogenic mutations causing severe, sporadic neurological disorders," senior author Michael Hammer, with the University of Arizona's Arizona Research Laboratories, and colleagues wrote. (genomeweb.com)
- Tester D, Will M, Haglund C, Ackerman M. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. (labome.org)
- Since most drugs which block sodium channels target the open state of the channel, and the fast inactivation-deficient mutations extend the time the open state exists, the variants allow drug candidate molecules to bind more effectively and allow researchers an extended amount of time in which to study the interaction of the drug with the channel. (albany.edu)
- The purpose of this study is to determine whether late sodium channel blockade might be effective in shortening the QTc interval in various LQT3 mutations and be considered as a safe therapeutic option for LQT3 patients. (clinicaltrials.gov)
- LQT3 mutations in the LQTS Registry will be studied using in vitro expression studies to determine whether ranolazine causes a decrease in late sodium current, slower recovery from inactivation and/or changes in time course of inactivation, ameliorating the causative functional effect of each individual mutation. (clinicaltrials.gov)
- Moreover, mutations in this channel have been shown to cause a rare form of heritable hypertension (Liddle's syndrome), and genetic linkage studies show that the β- and γ-subunits are linked to systolic blood pressure. (aspetjournals.org)
- There is growing evidence indicating that mutations, changes in expression, or inappropriate modulation of these channels can lead to electrical instability of the cell membrane and inappropriate spontaneous activity observed during pathological states. (eurekaselect.com)
- Loss of function mutations in this ion channel result in congenital inability to experience pain due to reduced excitability of nociceptors. (mcgill.ca)
- Sequencing the Ocd lines revealed mutations within highly conserved regions of the para coding sequence, in the transmembrane segment S6 of domain III (I1545M and T1551I), and in the linker between domains III and IV (G1571R), the location of the channel inactivation gate. (genetics.org)
- The G1571R mutation is of particular interest as mutations of the orthologous residue (G1306) in the human skeletal muscle sodium channel gene SCN4A are associated with cases of periodic paralysis and myotonia, including the human cold-sensitive disorder paramyotonia congenita . (genetics.org)
- The mechanisms by which sodium channel mutations cause cold sensitivity are not well understood. (genetics.org)
- These disorders are caused by mutations in the CLCN1 gene, which encodes the major muscle voltage-gated chloride channel [ 2 ]. (iospress.com)
- All three can be caused by mutations in the SCN4A gene, which is located on chromosome 17 and codes for the alpha subunit of the voltage-dependent sodium channel. (iospress.com)
- The apical membrane of many tight epithelia contains sodium channels that are primarily characterised by their high affinity to the diuretic blocker amiloride [ PMID: 8181670 , PMID: 8905643 , PMID: 8905643 , PMID: 7499195 ]. (ebi.ac.uk)
- What Is a Sodium Channel Blocker? (wisegeek.com)
- A sodium channel blocker is a medication that is categorized as a Class I antiarrhythmic drug. (wisegeek.com)
- The doctor may sometimes inject a sodium channel blocker into an intravenous drip. (wisegeek.com)
- People taking a sodium channel blocker may experience some side effects, which should be reported to the prescribing physician if they become severe. (wisegeek.com)
- Typically, a sodium channel blocker may cause dizziness , nausea, and vomiting , along with diarrhea or constipation. (wisegeek.com)
- Patients should be aware that a sodium channel blocker drug can cause chest pain, jaundice, and pain in the upper right area of the stomach. (wisegeek.com)
- The doctor may instruct the patient to take certain precautions while using a sodium channel blocker. (wisegeek.com)
- Before taking a sodium channel blocker, patients must disclose their other medical conditions, medications, and supplements. (wisegeek.com)
- The apical membranes of many tight epithelia contain sodium channels that are characterized primarily by their high affinity for the diuretic blocker amiloride. (wikipedia.org)
- Carbamazepine (Carbatrol) is a sodium channel blocker with IC50 of 131 μM in rat brain synaptosomes. (selleckchem.com)
- Also called sodium channel blocker. (thefreedictionary.com)
- In this study, we investigated the ability of sodium channel blocker, A-803467 to reverse ABCG2-mediated MDR. (aacrjournals.org)
- The open, activated channel creates the high-affinity binding site for these sodium channel blocker drugs, and block may be mainly electrostatic. (aspetjournals.org)
- Sodium channels can often be isolated from cells as a complex of two types of protein subunits, α and β. (bionity.com)
- When the α subunit protein is expressed by a cell, it is able to form channels which conduct Na + in a voltage-gated way, even if β subunits are not expressed. (bionity.com)
- The race to develop analgesic drugs that inhibit sodium channel Na V 1.7 is revealing a complex sensory role for the protein. (the-scientist.com)
- We conclude that ion selectivity in a K(+) channel is a property of size-matched ion binding sites created by the protein structure. (rcsb.org)
- Aronica E, Troost D, Rozemuller AJ, Yankaya B, Jansen GH, Isom LL, Gorter JA (2003) Expression and regulation of voltage-gated sodium channel beta1 subunit protein in human gliosis-associated pathologies. (springer.com)
- The voltage-gated sodium channel protein family comprises nine large a-subunits, termed Nav 1.1 - 1.9, and four smaller b-subunits. (albany.edu)
- Co-immunoprecipitation experiments carried out with a pan-sodium channel antibody confirmed that the sodium channel was associated with proteins of the dystrophin associated protein complex (DAPC). (pubmedcentralcanada.ca)
- Sodium channel blockers are used in the treatment of cardiac arrhythmia . (wikipedia.org)
- Class Ib antiarrhythmic agents are sodium channel blockers. (wikipedia.org)
- The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action (see the image below). (medscape.com)
- Metoprolol and nadolol did not block Na V 1.5 indicating that sodium channel block is not a class effect of β-blockers. (frontiersin.org)
- These properties are reminiscent of several other known sodium channel blockers and suggested that vinpocetine may exhibit frequency-dependent block. (aspetjournals.org)
- Jensen, TS 2017, ' Selective sodium channel blockers in trigeminal neuralgia ' Lancet Neurology , vol 16, no. 4, pp. 255-256. (au.dk)
- These proteins can be mutated to cause neuronal degradation, and are also thought to form sodium channels. (ebi.ac.uk)
- S. Sariban-Sohraby , Role of G-Proteins in the Regulation of Apical Membrane Sodium Permeability by Aldosterone in Epithelia. (elsevier.com)
- Because of the differences in the amino acids responsible for ion selectivity, and because proteins are likely to be under strong evolutionary constraints along every point of their evolution ( 20 ), it has been suggested that channels with intermediate pore sequences may exist in extant taxa ( 3 , 21 ), and some invertebrate channels have been proposed as representatives of these intermediate states ( 21 , 22 ). (pnas.org)
- Voltage-gated sodium channel β1 and β2 subunits were discovered as auxiliary proteins that co-purify with pore-forming α subunits in brain. (springer.com)
- Work over the past 2 decades, however, has provided strong evidence that these proteins are not simply ancillary ion channel subunits, but are multifunctional signaling proteins in their own right, playing both conducting (channel modulatory) and nonconducting roles in cell signaling. (springer.com)
- Abriel H, Kass RS (2005) Regulation of the voltage-gated cardiac sodium channel Nav1.5 by interacting proteins. (springer.com)
- We carried out analyses of sodium channel glycosylation, phosphorylation, and association with other proteins. (pubmedcentralcanada.ca)
- As the rat model of CIM occurs in genetically normal rats, this hyperpolarized shift in sodium channel gating must be due to post-translational modification of sodium channels or an alteration in sodium channel association with other proteins that modify gating. (pubmedcentralcanada.ca)
- It shows that in one species of electric fish, circadian cues and social encounters regulate the movements of proteins called voltage-gated sodium channels - which are crucial for generating the electric field - in cells of the electric organ. (wordpress.com)
- They appear to encode the major subunits of two distinct Na+-channel proteins. (caltech.edu)
- Using a technique called atomic force microscopy, Dilshan Balasuriya, led by Professor Mike Edwardson in Cambridge's Department of Pharmacology, imaged individual 3 trimers and confirmed that the complete 3-subunit trimers cross-linked up to three sodium channel α-subunits. (eurekalert.org)
- Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease," Journal of Pharmacology and Experimental Therapeutics , vol. 329, no. 2, pp. 764-774, 2009. (hindawi.com)
- This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied. (springer.com)
- The ability to inactivate is thought to be due to a tethered plug (formed by domains III and IV of the alpha subunit), called an inactivation gate, that blocks the inside of the channel shortly after it has been activated. (bionity.com)
- Voltage-gated sodium channels normally consist of an alpha subunit which forms the ion conduction pore and one to two beta subunits which have several functions including modulation of channel gating. (bionity.com)
-  Expression of the alpha subunit alone is sufficient to produce a functional channel. (wikidoc.org)
- Expression of alternatively spliced sodium channel alpha-subunit genes. (labome.org)
- Your search returned 16 sodium voltage-gated channel alpha subunit 8 Biomolecules across 6 suppliers. (biocompare.com)
- Molecular properties of epithelial, amiloride-blockable Na+ channels. (ebi.ac.uk)
- Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel. (ebi.ac.uk)
- However, the molecular mechanism by which these drugs block the channel has not been established. (pnas.org)
- The voltage-sensing domains have also shifted around the perimeter of the pore module in wild-type Na V Ab, compared to the mutant channel, and local structural changes identify a conserved interaction network that connects distant molecular determinants involved in Na V channel gating and inactivation. (nature.com)
- Vilin, Y. Y. & Ruben, P. C. Slow inactivation in voltage-gated sodium channels: molecular substrates and contributions to channelopathies. (nature.com)
- Bean BP (2005) The molecular machinery of resurgent sodium current revealed. (springer.com)
- We are studying the role of altered sodium channel expression in animal models of both partial and generalized seizures using in vivo and in vitro electrophysiology recordings and molecular techniques. (yale.edu)
- Molecular identity of dendritic voltage-gated sodium channels. (semanticscholar.org)
- This review provides an overview on how spider knottins modulate NaV channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. (unboundmedicine.com)
- however, we do not know if some TTX-R Na + channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. (dovepress.com)
- This summary article presents an overview of the molecular relationships among the voltage-gated sodium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels . (aspetjournals.org)
- At the molecular level, we identified a Na + channel and a Na + /H + exchanger (NHE) in the skin of N. obscura , where the NHE was up-regulated when acclimated to extremely low [Na + ] (0.05 mmol l −1 , pH 5) conditions. (biologists.org)
- A number of cell types are known to express tetrodotoxin-resistant (TTXr) sodium conductances, the molecular bases of which have remained elusive until recently. (aspetjournals.org)
- Calmodulin also serves as the Ca2+-sensing element, and the molecular mechanism is uncannily similar to that in calcium channels. (jhu.edu)
- The newly revealed molecular mechanisms will critically aid the long search for pharmaceuticals that specifically target Ca2+ feedback regulation of these channels. (jhu.edu)
- The findings also comment on where ion channels came from, and highlight new approaches to disease that may emerge by viewing diverse sodium and calcium channels through the lens of a unified molecular perspective. (jhu.edu)
- Therefore, in the absence of suitable vertebrate models, Ocd provides a system in which genetic, molecular, physiological, and behavioral tools can be exploited to determine mechanisms underlying sodium channel periodic paralyses. (genetics.org)
- A variety of different isoforms of mammalian voltage-gated sodium channels have been identified. (semanticscholar.org)
- An increasing body of literature indicates that regulation of firing behaviour in these cells is linked to their patterns of expression of specific sodium channel isoforms, which have been discovered to possess distinct biophysical characteristics. (ovid.com)
- A major contributor to the increase in inactivation is a hyperpolarized shift in the voltage dependence of inactivation of the adult (Na V 1.4) and embryonic (Na V 1.5) skeletal muscle sodium channel isoforms expressed in CIM muscle [ 9 ]. (pubmedcentralcanada.ca)
- The present findings contribute to our understanding of the mechanism of toxin-sodium channel interaction and provide a useful tool for the investigation of the structure and function of sodium channel isoforms and for the development of analgesics. (unboundmedicine.com)
- Phylogenetic analysis clusters the genes for these channels with other known sodium channels. (pnas.org)
- The two-dozen variants that remained were tested by Sanger sequencing, which verified just one de novo variant in the affected child: a missense mutation in SCN8A, the latest in a string of sodium channel genes that have been linked to epileptic conditions. (genomeweb.com)
- Mori N, Schoenherr C, Vandenbergh D, Anderson D. A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells. (labome.org)
- Sequence comparisons suggest that two Na+-channel genes arose early in evolution, before the divergence of vertebrate and invertebrate lines. (caltech.edu)
- A search of the genome of a single-celled choanoflagellate (the sister group of animals) identified a gene that is homologous to animal sodium channels and has a putative ion selectivity filter intermediate between calcium and sodium channels. (pnas.org)
- NEW YORK (GenomeWeb News) - By sequencing the genomes of four individuals from a single family, researchers from the University of Arizona and elsewhere have identified another sodium channel gene with ties to epilepsy - the fifth so far. (genomeweb.com)
- Researchers at Emory University have identified a specific mutation in a sodium channel gene (SCN1A) that is associated with epilepsy syndrome in a family. (innovations-report.com)
- Identifying this novel mutation in a sodium channel gene (SCN1A) on Chromosome 2, which is associated with epilepsy will, in the end, help us learn how to better treat patients and their families who have a type of familial epilepsy called generalized epilepsy with febrile seizures plus (GEFS+). (innovations-report.com)
- LQTS mutation N1325S in cardiac sodium channel gene SCN5A causes cardiomyocyte apoptosis, cardiac fibrosis and contractile dysfunction in mice. (labome.org)
- An excellent example is the voltage gated ion channel NaV 1.7 encoded by the gene SCN9a. (mcgill.ca)
- The para gene encodes a voltage-gated sodium channel. (genetics.org)
- The SCN7A gene encodes an atypical sodium channel (Nax), which is involved in osmoregulation via a sensing mechanism for the extracellular sodium concentration. (uva.nl)
- Regulation of the epithelial sodium channel by serine proteases in human airways," Journal of Biological Chemistry , vol. 277, no. 10, pp. 8338-8345, 2002. (hindawi.com)
- J.A. Schafer, L. Li, D. Sun, R.G. Morris, and T.W. Wilborn , Regulation of Amiloride-Sensitive Na+ Channels in the Renal Collecting Duct. (elsevier.com)
- P.R. Smith , cAMP Mediated Regulation of Amiloride-Sensitive Sodium Channels: Channel Activation or Channel Recruitment? (elsevier.com)
- Epithelial Na+ channels (ENaCs) in the brain play a significant role in the regulation of blood pressure. (wikipedia.org)
- The dynamic regulation of Na v 1.7 suggests that this channel contributes to neuronal hyperexcitability leading to inflammatory pain. (jneurosci.org)
- Aman TK, Grieco-Calub TM, Chen C, Rusconi R, Slat EA, Isom LL, Raman IM (2009) Regulation of persistent Na current by interactions between beta subunits of voltage-gated Na channels. (springer.com)
- Brackenbury WJ, Calhoun JD, Chen C, Miyazaki H, Nukina N, Oyama F, Ranscht B, Isom LL (2010) Functional reciprocity between Na + channel Nav1.6 and beta1 subunits in the coordinated regulation of excitability and neurite outgrowth. (springer.com)
- NOS1-dependent negative feedback regulation of the epithelial sodium channel in the collecting duct. (medworm.com)
- Out of this apparently diverse landscape comes a surprising yet fundamental unity in function amongst sodium and calcium channels, as described in a paper by the Calcium Signals Lab that appears in the 19 June 2014 issue of the journal Cell (paper entitled Conservation of Ca2+/calmodulin regulation across Na and Ca2+ channels ). (jhu.edu)
- In so doing, they revealed that the similarity region of these channels also gives rise to a strong Ca2+-dependent regulation of sodium channel opening. (jhu.edu)
- Hence, channel subunit diversity in a single animal is likely to represent diversity in activating stimuli and/or complex channel regulation. (g3journal.org)
- In the last decade, the idea of common organization of certain ion channel families exhibiting diverse physiological and pharmacological properties has received strong experimental support. (nih.gov)
- Voltage-gated sodium channels are established pharmacological targets for local anesthetics and many other drugs with shared mechanisms of action including certain anti-arrhythmic and anti-epilepsy agents. (frontiersin.org)
- This review describes the biochemical, biophysical and pharmacological properties of neuronal voltage-gated sodium channels (VGSC) and their implication in several neurological disorders. (eurekaselect.com)
- Therefore we are very happy that we now have a pharmacological tool that acts primarily on this type of channel," Schönberger explains. (phys.org)
- Vinpocetine is a clinically used synthetic vincamine derivative with a diverse pharmacological profile that includes action at several ion channels, principally "generic" populations of sodium channels that give rise to tetrodotoxin-sensitive conductances. (aspetjournals.org)
- Voltage-gated sodium channels (Na V ) are a particularly attractive pharmacological target as they are involved in almost all physiological processes including action potential generation and conduction. (mdpi.com)
- Potassium, sodium, calcium and glutamate-gated channels: pore architecture and ligand action. (nih.gov)
- Comparisons to previous open-pore potassium channel structures indicate that the voltage-sensor domains and the S4-S5 linkers dilate the central pore by pivoting together around a hinge at the base of the pore module. (nih.gov)
- Here, we discuss evidence that sodium channel β subunits not only regulate sodium channel function and localization but also modulate voltage-gated potassium channels. (springer.com)
- Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. (ovid.com)
- Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. (ovid.com)
- Calcium has been shown to block sodium channels  which explains the effects of hypercalcemia and hypocalcemia . (wikipedia.org)
- Voltage-dependent sodium channels are believed to have evolved from calcium channels at the origin of the nervous system. (pnas.org)
- Voltage-dependent calcium (Ca v ) channels evolved in single-celled eukaryotes and were used for intracellular signaling. (pnas.org)
- It has been hypothesized that Na v channels were derived from Ca v channels at the origin of the nervous system ( 3 ), thereby conferring the ability to conduct action potentials without interfering with intracellular calcium. (pnas.org)
- Calcium channels do not have a similar motif at the homologous region. (pnas.org)
- Nomenclature and structure-function relationships of voltage-gated calcium channels. (semanticscholar.org)
- Sodium and calcium ion channels comprise two distinct types of molecules that are absolutely critical to our lives. (jhu.edu)
- By contrast, calcium channels amplify the actions of these electrical signals by conducting Ca2+ ion flow into cells, which directly orchestrates brain communication and outright heart contraction. (jhu.edu)
- Despite the distinctive designs of these molecules, a long-standing curiosity has been the eerie similarity of a portion of sodium and calcium channels. (jhu.edu)
- This similarity region perhaps hints at the presence of a common functional module in both sodium and calcium channels. (jhu.edu)
- By contrast, for calcium channels, the corresponding region supports an important form of biological feedback control, whereby rising Ca2+ levels in cells throttle the opening of calcium channels, thus maintaining an appropriate level of Ca2+. (jhu.edu)
- The authors conclude that sodium and calcium channel families do harbor a common and vital Ca2+ feedback module, one that has persisted for more than a billion years of living history, when the designs of sodium and calcium channels first differentiated within the ancestors of the one-celled creature Paramecia . (jhu.edu)
- This likely lineage is artistically portrayed in the stylized phylogenetic branching of sodium and calcium channels. (jhu.edu)
- In all, valuable treatment secrets to heart arrhythmias, skeletal muscle myotonias, and neurodegeneration may well reside within the common feedback module of sodium and calcium channel families. (jhu.edu)
- Membrane topology of the amiloride-sensitive epithelial sodium channel. (ebi.ac.uk)
- Thus, in pigment cells, TPC2 mediates a PI(3,5)P2-activated melanosomal Na + channel to regulate pigmentation by modulating the melanosome's membrane voltage and pH. (nature.com)
- Another association between local anesthetics and the selectivity filter is the finding that the membrane-impermeant local anesthetic QX314 can block the cardiac Na + channel from the outside ( 12 ) and that this is probably due to access to the internal binding site through the pore ( 13 ). (pnas.org)
- Inactivation is a hallmark of Na V channel function and is critical for control of membrane excitability 3 , but the structural basis for this process has remained elusive. (nature.com)
- Local anesthetics block the generation and conduction of nerve impulses by inhibiting the current through voltage-gated Na + channels in the nerve cell membrane. (ahajournals.org)
- Prior to myelination (and following demyelination) sodium channels are present throughout the axon membrane at low density. (rochester.edu)
- The membrane topology of each subunit predicts the presence of two transmembrane domains (M1 and M2), a large extracellular loop (~70% of the size of the channel) and relatively short amino and carboxyl termini. (intechopen.com)
- All cells use a complex array of ion channels to maintain the appropriate ionic gradients across membrane barriers, including the plasma membrane and intracellular compartments and organelles. (pubmedcentralcanada.ca)
- Ion channels and neurotransmitter receptors are then packaged into vesicles, which are stored in reservoirs near the cell membrane. (wordpress.com)
- Gating of the channel is initiated by movement of the four charged S4 segments in the membrane electric field, leading to opening of the activation gate ( Hille, 2001 ). (aspetjournals.org)
- Sodium channel inhibitor insecticides are an emerging class of neurotoxic insect control agents that selectively inhibit voltage-gated sodium channels at membrane potentials that promote slow sodium channel inactivation. (cornell.edu)
- Metaflumizone shifted the voltage dependence of slow inactivation in the direction of hyperpolarization and selectively inhibited mammalian sodium channels at membrane potentials that facilitated slow inactivation. (cornell.edu)
- Mutation of the putative domain III selectivity filter residue of the adult rat skeletal muscle Na + channel (μ1) K1237E increased resting lidocaine block, but no change was observed in block by neutral analogs of lidocaine. (pnas.org)
- In this case, the patient's missense mutation is predicted to swap out an asparagine for an aspartate in a highly conserved region of a sodium channel sub-unit called Nav1.6 that's found throughout the brain and central nervous system. (genomeweb.com)
- Substitutions at V787 had residue- and compound-specific effects on the actions of sodium channel inhibitor insecticides that were independent of mutation-induced changes in slow inactivation. (cornell.edu)
- New Cambridge research provides fresh and unexpected insight into the structure of sodium channels and, specifically, one of its components - β-subunit molecules - which are responsible for 'fine-tuning' the activity of the channel. (eurekalert.org)
- The sodium channel lies on the surface of the nerve and muscle cells and is composed of a large molecule called the α-subunit, together with smaller β-subunit molecules. (eurekalert.org)
- This region of the 3-subunit lies on the outside of the cell and binds to the heart sodium channel α-subunit. (eurekalert.org)
- Epithelial Na + channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the γ -subunit," Journal of Biological Chemistry , vol. 282, no. 9, pp. 6153-6160, 2007. (hindawi.com)
- Writing in the June 18 online edition of Nature Cell Biology, the researchers show that BACE cleaves the β2 regulatory subunit of the Nav1 sodium channel. (alzforum.org)
- Voltage-gated sodium channels are composed of a pore-forming α subunit, and one or two regulatory β subunits. (alzforum.org)
- The Na + channel α-subunit consists of four homologous domains, each containing six transmembrane segments, S1-S6 ( 4 , 5 ). (pnas.org)
- An α subunit forms the core of the channel. (bionity.com)
- Brackenbury WJ, Davis TH, Chen C, Slat EA, Detrow MJ, Dickendesher TL, Ranscht B, Isom LL (2008) Voltage-gated Na + channel beta1 subunit-mediated neurite outgrowth requires Fyn kinase and contributes to postnatal CNS development in vivo. (springer.com)
- Diagram of a voltage-sensitive sodium channel α-subunit. (wikidoc.org)
- Each a-subunit alone is able to form a functional channel. (albany.edu)
- Each sodium channel is formed by one α-subunit and one or more β-subunits. (eurekaselect.com)
- A phosphorylation site at serine 487 was identified on the Na V 1.4 sodium channel α subunit, but there was no clear evidence of altered phosphorylation in the disease. (pubmedcentralcanada.ca)
- Here we identify two-pore channel 2 (TPC2) as the first reported melanosomal cation conductance by directly patch-clamping skin and eye melanosomes. (nature.com)
- Here, using direct patch-clamp recordings from skin and eye melanosomes, we report the first melanosomal cation conductance mediated by two-pore channel 2 (TPC2). (nature.com)
- Neo-saxitoxin and tetrodotoxin, which occlude the channel pore, reduced the amount of QX314 bound in D400A and A1529D, respectively. (pnas.org)
- Biophysical evidence suggests that the local anesthetic binding site is on the cytoplasmic side of the channel pore, lying between the selectivity filter and the channel gates ( 8 ). (pnas.org)
- 9 ) demonstrated that quaternary ammonium molecules containing aliphatic chains bind and block Shaker K + channels by interacting with two parts of the K + channel inner pore, the P loop near the channel's selectivity filter and the S6 segment. (pnas.org)
- The Shaker K + channel is thought to have a pore structure analogous to that of the Na + channel. (pnas.org)
- Ca v and Na v channels have four domains, each of which has a pore loop ( Fig. 1 ). (pnas.org)
- Ca v channels have acidic residues (E and D) in the pore of domains I-IV (usually E/E/E/E or E/E/D/D). Selectivity for sodium, on the other hand, is based on the residues D/E/K/A in the pore. (pnas.org)
- Sodium channels also have a cytoplasmic loop between their third and fourth domains that swings up and occludes the channel pore just milliseconds after activation ( Fig. 1 ). (pnas.org)
- Transmembrane topologies and patterns of the pore-facing residues are conserved in P-loop channels that include high-selective cation channels and certain ligand-gated channels. (nih.gov)
- Here we report the crystal structure of a voltage-gated Na(+) channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 Å resolution. (nih.gov)
- a, Pore-lining S6 helices of NavAb (yellow) and the closed MlotiK (3BEH), KcsA (1K4C) and NaK (2AHY) channels. (nih.gov)
- A transmembrane ion channel , containing an aqueous pore around 0.4nm diameter , with a negatively charged region internally (the selectivity filter ) to block passage of anions . (biology-online.org)
- Voltage-gated sodium (Na + ) channels are targets for local anesthetic (LA) drugs that bind in the inner pore of the channel with affinities related to the channel gating states. (aspetjournals.org)
- The channel's activation gate in this closed channel structure is located near the inner mouth of the pore, and it includes hydrophobic residues from the four S6 segments. (aspetjournals.org)
- LA drugs block the Na + channel pore, accessing their binding site in nerve and skeletal muscle mainly or entirely from the cytoplasm through the inner pore ( Narahashi and Frazier, 1971 ). (aspetjournals.org)
- Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. (uniprot.org)
- Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV channels in diseases, including chronic pain. (unboundmedicine.com)
- any of a class of antiarrhythmic agents that prevent ectopic beats by acting on partially inactivated sodium channels to inhibit abnormal depolarizations. (thefreedictionary.com)
- Rudy, B. Slow inactivation of the sodium conductance in squid giant axons. (nature.com)
- Armstrong, C. M., Bezanilla, F. & Rojas, E. Destruction of sodium conductance inactivation in squid axons perfused with pronase. (nature.com)
- Lymphocytes from individuals with this variant channel show an increased sodium conductance in response to cAMP in vitro. (aspetjournals.org)
- Ion-permeable channels often derive their generic names from the specialized conductance and permeability properties they possess, the voltage-dependent Na + channel being no exception. (springer.com)
- Using the voltage-dependent Na + channel as an example, we show in this chapter that, even though the lipid bilayer system offers many experimental advantages, the determination and the analysis of single-channel conductance and permeability data are not always simple. (springer.com)
Inactivation of the sodium2
- Data on binding sites and mechanisms of action of ligands of K+, Na+, Ca2+ and glutamate gated ion channels are considered in view of their possible structural similarity to the bacterial K+ channels. (nih.gov)
- Emphasized are structural determinants of ligand-receptor interactions within the channels and mechanisms of state-dependent action of the ligands. (nih.gov)
- Two primary mechanisms regulate this fluid layer: Starling's forces and active sodium (Na + ) transport. (frontiersin.org)
- Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses. (ovid.com)
- Apart from their use in identifying ion channels, measurements of ion selectivities and single-channel conductances also provide insight into the biophysical mechanisms underlying ion permeation through the channels. (springer.com)
- The results also suggest that neurophysiologic mechanisms of morphine tolerance and visceral hyperalgesia are related at the TTX-R Na + channel. (dovepress.com)
- Additionally, we found that leeches in dilute freshwater environments use both a vacuolar-type H + -ATPase (VHA)-assisted uptake via a Na + channel and a NHE-based mechanisms for Na + uptake. (biologists.org)
- To our knowledge, this is the first study showing the mechanisms of Na + uptake and their links to ammonia excretion in a freshwater invertebrate, where results suggest an ammonia-independent Na + uptake mechanism relying on both Na + channels and NHEs. (biologists.org)
- Short extreme depolarizations partially activated the toxin-bound channel, indicating voltage-dependent inhibition of HNTX-III. (unboundmedicine.com)
- Vinpocetine produced a concentration- and state-dependent inhibition of Na V 1.8 sodium channel activity. (aspetjournals.org)
- Metaflumizone, a newly-commercialized insecticide in the animal health market, causes state-dependent inhibition of insect sodium channels. (cornell.edu)
- I substituted alanine, cysteine, or lysine for residue V787 in DII-S6 of Nav1.4 channels to test the hypothesis that the extent of insecticide inhibition is directly related to the availability of slow-inactivated sodium channels. (cornell.edu)
- Dr Chirgadze added: "Our research has important implications for our understanding of the mechanism of sodium channel behaviour. (eurekalert.org)
- Some antiepileptic drugs work by acting on combination of channels or through some unknown mechanism of action. (medscape.com)
- Acquired sodium channelopathy may be the mechanism underlying acute neuropathy in critically ill patients. (jci.org)
- These results imply that V787 is part of or in close proximity to the binding site for sodium channel inhibitor insecticides on mammalian voltage-gated sodium channels, which may not be identical for all members of this insecticide class. (cornell.edu)
- Past theoretical work and recent experimental evidence have suggested that spines could contain sodium channels. (columbia.edu)
- Immunoprecipitations were performed with a pan-sodium channel antibody, and the resulting complexes probed in Western blots with various antibodies. (pubmedcentralcanada.ca)
- Class Ib drugs tend to be more specific for voltage gated Na channels than Ia. (wikipedia.org)
- Dudel, J., and Rudel, R., Voltage and time dependence of excitatory sodium current in cooled sheep Purkinje fibers. (springer.com)
- The researchers looked at sodium channel function by whole-cell voltage-clamp recording in B104 cells stably expressing β2 or β2 plus BACE1. (alzforum.org)
- These drugs work by blocking voltage-gated Na + channels ( 1 - 3 ). (pnas.org)
- The crystal structure of a voltage-gated sodium channel. (nih.gov)
- The voltage sensitivity of this channel is due to positive amino acids located at every third position. (bionity.com)
- Voltage-gated sodium channels have three types of states: deactivated (closed), activated (open), and inactivated (closed). (bionity.com)
- Since the mid-2000s, the voltage-gated sodium channel Na V 1.7 has emerged as a promising target for a new class of analgesics. (the-scientist.com)
- Our data suggest that a hyperpolarized shift in the voltage dependence of sodium channel inactivation causes increased sodium inactivation and reduced excitability. (jci.org)
- A prokaryotic voltage-gated sodium channel. (nature.com)
- Scn8a channels inactivated more rapidly and showed differences in their voltage-dependent properties compared with Rat1 and Rat2 when only the α subunits were expressed. (jneurosci.org)
- Therefore, all three channels showed similar voltage dependence and inactivation kinetics in the presence of the β subunits. (jneurosci.org)
- Thus, we investigated whether Slo2 channels bind to PSD-95, because it is well known that other types of K+ channels, voltage-gated and inward rectifier K+ channels, bind to PSD-95 via the PDZ binding motif and are involved in excitatory synaptic transmission. (nih.gov)
- Brackenbury WJ (2012) Voltage-gated sodium channels and metastatic disease. (springer.com)
- Fairey E, Bottein Dechraoui M, Sheets M, Ramsdell J. Modification of the cell based assay for brevetoxins using human cardiac voltage dependent sodium channels expressed in HEK-293 cells. (labome.org)
- The expression of voltage dependent sodium channels in HEK cells is anticipated to provide enhanced performance for cell-based detection of toxins for drug and natural product discovery, biomonitoring and environmental monitoring. (labome.org)
- Payandeh J, Gamal El Din T, Scheuer T, Zheng N, Catterall W. Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. (labome.org)
- Methods and Results The inhibitory effects on the cardiac sodium current (I Na ) of 10 μmol/L R (+)- and S (−)-bupivacaine were investigated by use of the whole-cell voltage clamp technique in isolated guinea pig ventricular myocytes. (ahajournals.org)
- 1 2 3 Nevertheless, all voltage-gated Na + channels exposed to sufficient concentrations of these agents will be affected. (ahajournals.org)
- Therapeutics treat a variety of diseases by targeting specific voltage-gated sodium (Nav) channels, and new drugs are continually being developed to improve both the safety and efficacy of treating Nav-related diseases. (albany.edu)
- Carbamazepine inhibits the binding of [ 3 H]batrachotoxinin A 20-α-benzoate (BTX-B) to a receptor site of voltage-sensitive sodium channel with IC50 of 131 μM, to decrease the activation of sodium channel ion flux in rat brain synaptosomes. (selleckchem.com)
- Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. (springer.com)
- The channel is voltage gated: it opens in response to a small depolarisation of the cell (usually caused by an approaching action potential ), by a multistep process . (biology-online.org)
- The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. (semanticscholar.org)
- Inherited disorders of voltage-gated sodium channels. (semanticscholar.org)
- Nomenclature and structure-function relationships of voltage-gated sodium channels. (semanticscholar.org)
- A superfamily of voltage-gated sodium channels in bacteria. (semanticscholar.org)
- Diversity of mammalian voltage-gated sodium channels. (semanticscholar.org)
- Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. (unboundmedicine.com)
- Phenytoin is an inactive voltage-gated sodium channel stabilizer. (selleckchem.com)
- Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage-gated Na channels due to the chronic administration of these medications. (dovepress.com)
- A major contributor to this sodium channel inactivation is a hyperpolarized shift in the voltage dependence of sodium channel inactivation. (pubmedcentralcanada.ca)
- Based on this approach, it should be possible to develop an optically based screening platform for voltage-sensitive ion channels. (phys.org)
- It is a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels. (unboundmedicine.com)
- Vinpocetine also produced an ∼22 mV leftward shift in the voltage dependence of Na V 1.8 channel inactivation but did not affect the voltage range of channel activation. (aspetjournals.org)
- The mouse Scn8a sodium channel and its ortholog Na6 in the rat are abundantly expressed in the CNS. (jneurosci.org)
- To examine the functional characteristics of this channel, we constructed a full-length cDNA clone encoding the mouse Scn8a sodium channel and expressed it in Xenopus oocytes. (jneurosci.org)
- The electrophysiological properties of the Scn8a channels were compared with those of the Rat1 and Rat2 sodium channels. (jneurosci.org)
- Scn8a channels were sensitive to tetrodotoxin at a level comparable to that of Rat1 or Rat2. (jneurosci.org)
- Coexpression of the β 1 and β 2 subunits modulated the properties of Scn8a channels, but to a lesser extent than for the Rat1 or Rat2 channels. (jneurosci.org)
- Scn8a channels coexpressed with the β subunits exhibited a persistent current that became larger with increasing depolarization, which was not observed for either Rat1 or Rat2 channels. (jneurosci.org)
- The Scn8a/Rat6 and Rat1 channels may be responsible for distinct sodium conductances in Purkinje cells. (jneurosci.org)
- and RH-3421 and RH-4841, two experimental insecticides, on mammalian sodium channels using the Xenopus laevis oocyte expression system. (cornell.edu)
- Modulation of sodium channels of squid nerve membranes by grayanotoxin I. (aspetjournals.org)
- H. O'Brodovich, B. Rafii, A.K. Tanswell, and O. Pitkänen , Induction of Epithelial Sodium Channel Expression and Sodium Transport in Distal Lung Epithelia by Oxygen. (elsevier.com)
- suggested that inactivating and persistent sodium conductances in Purkinje cells result from expression of Rat1 and Rat6, respectively. (jneurosci.org)
- One such TTXr channel, termed Na V 1.8, is of particular interest because of its prominent and selective expression in peripheral afferent nerves. (aspetjournals.org)
- Conclusions: The increased and persistent expression of SCN7A/Nax in the epileptic rat and human hippocampus supports the possible involvement of this channel in the complex reorganization occurring within the hippocampus during the epileptogenic process in TLE. (uva.nl)
- The results demonstrate that the Na + channel selectivity filter is involved in interactions with the hydrophilic part of the drugs, and it normally limits extracellular access to and escape from their binding site just within the selectivity filter. (pnas.org)
- They also suggested that these aromatic residues might be spatially close to the Na + channel selectivity filter, which may compose part of the binding site ( 11 ). (pnas.org)
- These possible relationships between local anesthetics and the selectivity filter prompted us to investigate the roles of the selectivity filter in binding and access of the drugs by using mutagenesis of the adult rat skeletal muscle Na + channel (μ1). (pnas.org)
- From this phylogeny we infer ancestral states of the ion selectivity filter and show that this state has been retained in the choanoflagellate and placozoan channels. (pnas.org)
- This is because lidocaine selectively blocks Na channels in their open and inactive states and has little binding capability in the resting state. (wikipedia.org)
- The fast inactivation-deficient variants open normally but inactivate very slowly, remaining open at least a hundred times longer than does a wild-type channel. (albany.edu)
- In the example shown below, low concentrations of lidocaine had minimal effects on the peak channel response, but the effects on the late current response were much more pronounced. (albany.edu)
- Reabsorption is a two-step process: first, sodium enters via sodium-permeable channels in the apical membranes of alveolar type 1 and 2 cells followed by active extrusion of sodium into the interstitium by the basolateral Na + , K + -ATPase. (frontiersin.org)
- At night, low light levels and social interactions drive the insertion of sodium channels into the cell membranes, leading to a dramatic increase in the strength of the electric field. (wordpress.com)
Block sodium channels1
- Lamotrigine is known to block sodium channels but it is not known whether it is extracellular or intracellular. (wikipedia.org)