Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.
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.
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.
A voltage-gated sodium channel subtype found widely expressed in neurons of the central and peripheral nervous systems. Defects in the SCN8A gene which codes for the alpha subunit of this sodium channel are associated with ATAXIA and cognitive deficits.
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.
A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.
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.
A voltage-gated sodium channel subtype that is expressed in nociceptors, including spinal and trigeminal sensory neurons. It plays a role in the transmission of pain signals induced by cold, heat, and mechanical stimuli.
A class of drugs that stimulate sodium influx through cell membrane channels.
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.
A voltage-gated sodium channel subtype found widely expressed in nociceptive primary sensory neurons. Defects in the SCN9A gene, which codes for the alpha subunit of this sodium channel, are associated with several pain sensation-related disorders.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.
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 where the flow of K+ ions into the cell is greater than the outward flow.
Batrachotoxin is the 20-alpha-bromobenzoate of batrachotoxin A; they are toxins from the venom of a small Colombian frog, Phyllobates aurotaenia, cause release of acetylcholine, destruction of synaptic vesicles and depolarization of nerve and muscle fibers.
A voltage-gated sodium channel subtype found in neuronal tissue that mediates the sodium ion PERMEABILITY of excitable membranes.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.
A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.
Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.
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).
A voltage-gated sodium channel subtype found in the neurons of the NERVOUS SYSTEM and DORSAL ROOT GANGLIA. It may play a role in the generation of heat and mechanical pain hypersensitivity.
Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.
A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.
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.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
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.
A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.
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.
The ability of a substrate to allow the passage of ELECTRONS.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
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 whose activation is dependent on intracellular calcium concentrations.
A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.
A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.
A voltage-gated sodium channel beta subunit subtype that non-covalently associates with voltage-gated alpha subunits. Defects in the SCN3B gene which codes for this beta subunit are associated with Brugada syndrome 7.
The rate dynamics in chemical or physical systems.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
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.
Regularly spaced gaps in the myelin sheaths of peripheral axons. Ranvier's nodes allow saltatory conduction, that is, jumping of impulses from node to node, which is faster and more energetically favorable than continuous conduction.
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.
The active insecticidal constituent of CHRYSANTHEMUM CINERARIIFOLIUM flowers. Pyrethrin I is the pyretholone ester of chrysanthemummonocarboxylic acid and pyrethrin II is the pyretholone ester of chrysanthemumdicarboxylic acid monomethyl ester.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.
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.
A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.
A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.
A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.
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)
A voltage-gated sodium channel beta subunit subtype that covalently associates with voltage-gated alpha subunits. Defects in the SCN4B gene, which codes for this beta subunit, are associated with long QT syndrome-10.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
A voltage-gated sodium channel beta subunit that binds covalently to voltage-gated alpha subunits.
Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION CHANNELS.
Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
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)
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
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.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.
Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A ubiquitous sodium salt that is commonly used to season food.
Established cell cultures that have the potential to propagate indefinitely.
A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.
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.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.
A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.
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.
Toxic or poisonous substances elaborated by marine flora or fauna. They include also specific, characterized poisons or toxins for which there is no more specific heading, like those from poisonous FISHES.
The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.
Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.
A voltage-gated potassium channel that is expressed primarily in the HEART.
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.
A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.
A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.
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.
Venoms from jellyfish; CORALS; SEA ANEMONES; etc. They contain hemo-, cardio-, dermo- , and neuro-toxic substances and probably ENZYMES. They include palytoxin, sarcophine, and anthopleurine.
Proteins obtained from species in the class of AMPHIBIANS.
A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
A genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel.
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.
Elements of limited time intervals, contributing to particular results or situations.
Polycyclic ethers produced by Gambierdiscus (DINOFLAGELLATES) from gambiertoxins, which are ingested by fish which in turn may be ingested by humans who are susceptible to the CIGUATERA POISONING.
Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.
A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly.
Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
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)
A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.
A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
Use of electric potential or currents to elicit biological responses.
A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.
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.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
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.
The physical characteristics and processes of biological systems.
A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
The hollow, muscular organ that maintains the circulation of the blood.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of Bellini) which opens on the summit of the papilla.
An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
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.
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.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
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.
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.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is closely related to KCNQ2 POTASSIUM CHANNEL. It is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
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).
A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
The order Actiniaria, in the class ANTHOZOA, comprised of large, solitary polyps. All species are carnivorous.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
CALCIUM CHANNELS located in the neurons of the brain.
Stable sodium atoms that have the same atomic number as the element sodium, but differ in atomic weight. Na-23 is a stable sodium isotope.
A surface anesthetic that acts by preventing transmission of impulses along NERVE FIBERS and at NERVE ENDINGS.
A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.
An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
Contractile tissue that produces movement in animals.
An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry.
Proteins prepared by recombinant DNA technology.
CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
Compounds based on N-phenylacetamide, that are similar in structure to 2-PHENYLACETAMIDES. They are precursors of many other compounds. They were formerly used as ANALGESICS and ANTIPYRETICS, but often caused lethal METHEMOGLOBINEMIA.
Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.
A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions.
A genus in the family Blattidae containing several species, the most common being P. americana, the American cockroach.
A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.
A family of immunoglobulin-related cell adhesion molecules that are involved in NERVOUS SYSTEM patterning.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
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 subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
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.
A group of peptide antibiotics from BACILLUS brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D are linear. Gramicidin is one of the two principal components of TYROTHRICIN.
The electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electrical charges.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
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.
ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.
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)
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).

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 +info)

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)

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?
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 ...
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
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 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 ...
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 ...
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 ...
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 ...
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 ...
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]
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) ...
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 ...
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. ...
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 ...
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.. ...
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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 ...
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 ...
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
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 ...
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 ...
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), ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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?
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 …
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
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. ...
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
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.. ...
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, ...
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 ...
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.
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 ...
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, ...
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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.
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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
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 ...
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 ...
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 ...
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 gene is associated with atrial fibrillation.: Atrial fibrillation (AF) is one of the most common su
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 (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
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[-] ...
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 ...
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 ...
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
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 ...
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 ...
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. ...
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
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 ...
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 ...
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
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.
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 ...
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 ...
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
Enhanced Understanding of Ca2+ Modulation of the Human Cardiac Sodium Channel: Tight Binding of Calmodulin to the Inactivation ...
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 ...
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 ...
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)18 sodium channel blocker that attenuates neuropathic tactile allodynia in rats | Laser spine institute london ontariopost_content%%
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.
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 ...
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). ...
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 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 ...
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. 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...
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
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. ...
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.
As the cardiac sodium channel is the most pH-sensitive sodium channel, most of what is known is based on this channel. ... One such residue is C373 in the cardiac sodium channel which makes it the most pH-sensitive sodium channel among the sodium ... Most channels of this type are permeable to potassium to some degree as well as to sodium. Voltage-gated sodium channels play ... Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. ...
The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that ... and are also thought to form sodium channels. The epithelial sodium (Na+) channel (ENaC) family belongs to the ENaC/P2X ... Ion Channel Diseases Epithelial+sodium+channel at the US National Library of Medicine Medical Subject Headings (MeSH) This ... Horisberger JD, Chraïbi A (2004). "Epithelial sodium channel: a ligand-gated channel?". Nephron Physiology. 96 (2): 37-41. doi: ...
v t e (All stub articles, Pharmacology stubs, Ion channel openers, Sodium channels, Sodium channel openers). ... A sodium channel opener is a type of drug which facilitates ion transmission through sodium channels. Examples include toxins, ... which activates the epithelial sodium channel (ENaC). Sodium channel blocker Shabbir W, Tzotzos S, Bedak M, Aufy M, Willam A, ... "Glycosylation-dependent activation of epithelial sodium channel by solnatide". Biochem. Pharmacol. 98 (4): 740-53. doi:10.1016/ ...
... s are drugs which impair the conduction of sodium ions (Na+) through sodium channels. The following ... Sodium channel blockers are also used as local anesthetics and anticonvulsants. Sodium channel blockers have been proposed for ... Sodium channel opener Sodium+Channel+Blockers at the US National Library of Medicine Medical Subject Headings (MeSH) Armstrong ... promoting the inactivated conformation of sodium channels. Sodium channel blockers are used in the treatment of cardiac ...
An epithelial sodium channel blocker is a sodium channel blocker that is selective for the epithelial sodium channel. An ... v t e (Sodium channel blockers, All stub articles, Cardiovascular system drug stubs). ... Sagnella GA, Swift PA (2006). "The renal epithelial sodium channel: genetic heterogeneity and implications for the treatment of ...
Voltage gated sodium channels have used as therapeutic targets in various modes of research, allowing versutoxin to also be ... Both of these types of toxins bind specifically to site 3 on the sodium channel. Despite versutoxin having a ICK which both α- ... Versutoxin, in particular, is capable of affecting the voltage-gated sodium channels of prey. Studies conducted on primates ... The delta represents the main biological activity of the neurotoxin; inhibiting sodium channels. In more recent research, ...
Sodium channel β-subunit 4, also known as SCN4B or Naβ4, is an auxiliary sodium channel subunit that can alter the kinetics of ... Human Sodium channel subunit beta-4 (SCN4B)) at the PDBe-KB. (Genes on human chromosome 11, Sodium channels). ... "Entrez Gene: sodium channel". Medeiros-Domingo A, Kaku T, Tester DJ, Iturralde-Torres P, Itty A, Ye B, Valdivia C, Ueda K, ... 2003). "Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2". J. Neurosci. 23 (20): 7577-85 ...
... is a class 1a antiarrhythmic agent; a sodium channel blocker. It is an alkaloid and can be extracted from scotch ... thus is can be assumed that the enzyme catalyzes the formation of the quinolizidine skeleton in a channeled fashion . 7- ...
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 (ENaC) , Ion channels , IUPHAR/BPS Guide to PHARMACOLOGY". Enslow BT, ... This syndrome is caused by dysregulation of the epithelial sodium channel (ENaC) due to a genetic mutation at the 16p13-p12 ... The treatment is a potassium-sparing diuretic, such as amiloride, that directly blocks the sodium channel. Potassium-sparing ... "Genetic disorders of the collecting tubule sodium channel: Liddle's syndrome and pseudohypoaldosteronism type 1". UpToDate. ...
Voltage-gated sodium channels and calcium channels are made up of a single polypeptide with four homologous domains. Each ... Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and ... Sodium channels have similar functional properties across many different cell types. While ten human genes encoding for sodium ... this type of channel differs in function between cell types. Ca2+ channels produce action potentials similarly to Na+ channels ...
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 WA (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 ...
... 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++), ...
Some carbamates block sodium channels. Phenprobamate was used as an anxiolytic and is still sometimes used in Europe for ... The α2δ is found on L-type calcium channels, N-type calcium channels, P/Q-type calcium channels, and R-type calcium channels ... while N-type calcium channels are located throughout the central and peripheral nervous systems. N-type calcium channels are ... This causes chloride channels to open, allowing chloride to flood into the neuron, slowing down communication betwen neurons; ...
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 KB, Yuste R (July 2007). "Sodium channels amplify spine potentials". Proceedings of the ... February 2015). "Local postsynaptic voltage-gated sodium channel activation in dendritic spines of olfactory bulb granule cells ... we now suspect that there are voltage-dependent sodium, potassium, and calcium channels in the spine heads. Cable theory ... Ngo-Anh TJ, Bloodgood BL, Lin M, Sabatini BL, Maylie J, Adelman JP (May 2005). "SK channels and NMDA receptors form a Ca2+- ...
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 ...
September 2018). "Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development". ... sodium channels, "SCN3A"). Patients with autism have overall higher levels of cortical gyrification, but only in the temporal, ...
... this sodium ion channel coordinates the effects of this compound. Veratradine also activates additional Nav channels. These ... Non-protein ion channel toxins, Benzoate esters, Plant toxins, Secondary alcohols, Tertiary alcohols, Sodium channel openers). ... Veratridine inhibits sodium channel inactivation by shifting the activation threshold toward a more negative potential. The ... It binds to binding site 2 on the voltage-gated sodium channels (the same site bound by batrachotoxin, aconitine, and ...
Sodium channel subunit beta-1 is a protein that in humans is encoded by the SCN1B gene. Voltage-gated sodium channels are ... "Entrez Gene: SCN1B sodium channel, voltage-gated, type I, beta". Hartshorne RP, Catterall WA (1984). "The sodium channel from ... plus-associated sodium channel beta1 subunit mutations severely reduce beta subunit-mediated modulation of sodium channel ... 2002). "The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart ...
Sodium channel subunit beta-2 is a protein that in humans is encoded by the SCN2B gene. Sodium channel GRCh38: Ensembl release ... "Entrez Gene: SCN2B sodium channel, voltage-gated, type II, beta". Hartshorne RP, Catterall WA (1984). "The sodium channel from ... 1996). "Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif". ... Plummer NW, Meisler MH (May 1999). "Evolution and diversity of mammalian sodium channel genes". Genomics. 57 (2): 323-31. doi: ...
... is a sodium channel blocker. It binds preferentially to voltage-gated sodium channels in their inactive ... Nevitt SJ, Marson AG, Weston J, Tudur Smith C (August 2018). "Sodium valproate versus phenytoin monotherapy for epilepsy: an ... It has been suggested that carbamazepine can also block voltage-gated calcium channels, which will reduce neurotransmitter ... and calcium channel blockers. Grapefruit juice raises the bioavailability of carbamazepine by inhibiting the enzyme CYP3A4 in ...
These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group of ion ... Ren D, Navarro B, Xu H, Yue L, Shi Q, Clapham DE (December 2001). "A prokaryotic voltage-gated sodium channel". Science. 294 ( ... Payandeh J, Scheuer T, Zheng N, Catterall WA (July 2011). "The crystal structure of a voltage-gated sodium channel". Nature. ... The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. ...
TTX-s Na+ channels) and tetrodotoxin-resistant voltage-gated sodium channels (TTX-r Na+ channels). Tetrodotoxin inhibits TTX-s ... Sodium channel blockers, Orthoesters, Adamantane-like molecules, Secondary metabolites, Analgesics, Non-protein ion channel ... Tetrodotoxin is a sodium channel blocker. It inhibits the firing of action potentials in neurons by binding to the voltage- ... gated sodium channels in nerve cell membranes and blocking the passage of sodium ions (responsible for the rising phase of an ...
No sodium channel characteristics were altered. Hence, basic membrane properties were changed due to the modified conductance ... ratio of potassium and sodium, and this change was temperature dependent. Part of the somatosensory cortex of rats is arranged ... potassium conductance while increasing the activation threshold and lowering the amplitude of voltage-gated potassium channels ...
... is a short-chained neurotoxin that causes the victim's sodium channels to have delayed inactivation, causing them ...
Voltage-gated sodium channels: Because it accumulates in synaptic vesicles, Risperidone inhibits voltage-gated sodium channels ... Brauner JM, Hessler S, Groemer TW, Alzheimer C, Huth T (April 2014). "Risperidone inhibits voltage-gated sodium channels". ...
In insects, DDT opens voltage-sensitive sodium ion channels in neurons, causing them to fire spontaneously, which leads to ... Insects with certain mutations in their sodium channel gene are resistant to DDT and similar insecticides. DDT resistance is ... Scott, Jeffrey G. (January 7, 2019). "Life and Death at the Voltage-Sensitive Sodium Channel: Evolution in Response to ... Dong, Ke (January 6, 2007). "Insect sodium channels and insecticide resistance". Invertebrate Neuroscience. 7 (1): 17-30. doi: ...
For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell ... Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at ... About 99% of a human's body weight is made up of the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen ... The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate and the organic ion bicarbonate. The ...
... there is a short-circuit channel (i.e. a highly K-permeable ion channel) for potassium in the membrane, thus the voltage across ... The sodium-potassium pump (sodium-potassium adenosine triphosphatase, also known as Na⁺/K⁺-ATPase, Na⁺/K⁺ pump, or sodium- ... Sodium,+Potassium+ATPase at the US National Library of Medicine Medical Subject Headings (MeSH) RCSB Protein Data Bank: Sodium- ... The sodium-potassium pump mechanism moves 3 sodium ions out and moves 2 potassium ions in, thus, in total, removing one ...
"The Turek Clinic YouTube Channel". Retrieved 11 May 2012. "Fertile Hope Medical Advisory Board". Retrieved 11 May 2012. Turek ... 50 mixture of 150 mosmol fructose and 150 mosmol sodium citrate. The tails of normal sperm will swell when exposed to this ...
Other potassium channels like large conductance calcium-dependent potassium channels and sodium chloride dependent potassium ... NALCN sodium leak channels have been hypothesized to give rise to an inward current that may play an important role in the ... Since NALCN sodium leak channels may contribute to the depolarization of neurons, their regulation by G-protein coupled ... These nonselective cation channels may provide a voltage-independent sodium current that also helps slightly depolarize neurons ...
Ca2+-activated K+ channels that open in response to the influx of Ca2+ during the action potential carry much of the K+ current ... Gulledge AT, Dasari S, Onoue K, Stephens EK, Hasse JM, Avesar D (2013). "A sodium-pump-mediated afterhyperpolarization in ... N. Gu, K. Vervaeke, H. Hu, and J.F. Storm, Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium ... Ca2+ Channels Involved in the Generation of the Slow Afterhyperpolarization in Cultured Rat Hippocampal Pyramidal Neurons. J ...
When the neuron is depolarizing, the CNG ion channel is open allowing sodium and calcium to rush into the cell. The influx of ... CaM will then bind to the CNG channel and close it, stopping the sodium and calcium influx. CaMKII will be activated by the ... opens ion channels in the cell membrane, resulting in an influx of sodium and calcium ions into the cell, and an efflux of ... Touhara, Kazushige (2009). "Insect Olfactory Receptor Complex Functions as a Ligand-gated Ionotropic Channel". Annals of the ...
The 9s electrons should have ionization energies comparable to those of the 3s electrons of sodium and magnesium, due to ... One calculation by Y. Gambhir et al., analyzing nuclear binding energy and stability in various decay channels, suggests a ...
... or a substitute such as a water solution of citric acid and sodium citrate at lime-juice strength. Mix together 1⁄4 drachm ( ... for distribution through official channels. Coca-Cola inventor John Pemberton is said to have written this recipe in his diary ...
Diagnosis is made by a FENa (fractional excretion of sodium) > 3% and presence of muddy casts (a type of granular cast) in ... Nephrology Channel. 2008. Retrieved 2008-09-23. Goldman, Lee; Cecil, Russell L. (2008). Cecil medicine. ...
... instead a unique cytotoxin called calliotoxin that causes near instantaneous paralysis by blocking the victims sodium channels ...
Subjects covered in the book include both traditional approaches to looking at arrhythmia, such as ion channel effects, and ... Novel ideas offered included studying sodium-calcium exchanger and ryanodine receptor effects. One chapter (5) is dedicated to ...
For example, if a person has a mutation in a gene that creates the sodium channel (a part of the neuron required for firing) it ...
"Can Sodium Save Nuclear Power?". Scientific American. Retrieved 24 November 2021. "Beyond ITER". The ITER Project. Information ... Play Film / Discovery Channel. (see 1996 interview with Mikhail Gorbachev) "Analysis: Nuclear renaissance could fizzle after ...
The main component in the tail is sodium, which has been detected beyond 24 million km (1000 RM) from the planet. This sodium ... During its 2009 flyby, the Ultraviolet and Visible Spectrometer (UVVS) channel of the Mercury Atmospheric and Surface ... The temperature for sodium is much higher, reaching 750-1,500 K on the equator and 1,500-3,500 K at the poles. Some ... A year after the sodium discovery, Potter and Morgan reported that potassium (K) is also present in the exosphere of Mercury, ...
... is also a potent blocker of voltage-gated sodium channels, and this action is thought to be involved in both its ... Bertelsen, Anne K.; Backonja, Misha-Miroslav (2007). "Drugs Targeting Voltage-Gated Sodium and Calcium Channels". Encyclopedia ... Sodium channel blockers, Tricyclic antidepressants, Wikipedia medicine articles ready to translate). ... August 2007). "Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin". Biochemical Pharmacology. 74 ...
However, a NASICON membrane is being considered for a sodium-sulfur battery where the sodium stays solid. The main application ... framework with open channels that endow it with the capability for fast ionic diffusion. A strong and lasting structural ... "Importance of Crystallographic Sites on Sodium-Ion Extraction from NASICON-Structured Cathodes for Sodium-Ion Batteries". ACS ... The development of sodium-ion batteries is important since it makes use of an earth-abundant material and can serve as an ...
Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (1998). "Interaction of muscle and brain sodium channels ... has been reported to bind to the C-terminal domain of murine cardiac voltage-gated sodium channels (SkM2) causing altering ion ... a disease of sodium channel disruption". Circ Arrhythmia Electrophysiol. 1 (3): 193-201. doi:10.1161/CIRCEP.108.769224. PMC ... "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated ...
Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R, Glickman MH, Finley D (Nov 2000). "A gated channel into the ... such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14. The proteasome and its subunits are of clinical ...
The result is an inward calcium and sodium current similar to capsaicin-evoked currents. TRPV1 channels may also have voltage- ... transient receptor potential cation channel A1), is important in thermal and pain detection. TRPV1 channels are activated by ... The specific mechanism behind heat-activation of TRPV1 channels has yet to be deciphered. TRPV1-S (TRPV1 short) is an isoform ... Deep sequencing of complementary DNA of these receptor channels shows that this is not true for closely related fruit bats ...
... is a voltage-gated sodium channel blocker with anticonvulsant and mood-stabilizing effects that is related to ...
K.L. Bai, J. Katz, On the refractive index of sodium iodide solutions for index matching in PIV, Exp. Fluids 55(4) (2014). S. ... C. Zhang, J. Wang, W. Blake, J. Katz, Deformation of compliant wall in a turbulent channel flow, Journal of Fluid Mechanics 823 ... S. Talapatra, J. Katz, Coherent structures in the inner part of a rough-wall channel flow resolved using holographic PIV, ... Enhancement of channel wall vibration due to acoustic excitation of an internal bubbly flow, J. Fluids Struct. 26(6) (2010) 994 ...
Sodium channel blockers, All stub articles, Cardiovascular system drug stubs). ...
... micro-oxic conditions and to use particular agar plates made by filtered seawater supplemented with sodium sulfide and sodium ... gliding and this movement is likely connected to string-like structures in the outer membrane and trans-peptidoglycan channels ...
... to absorption into human cells and production of nano-channels that obstruct vital ion channels that ferry potassium and sodium ... permeable channels and adverse action towards mammalian cells". FEBS Journal. 279 (22): 4172-4190. doi:10.1111/febs.12010. PMID ...
... leading to increased expression of the epithelial sodium channel (ENaC), which also promotes sodium re absorption. WNK1 ... and large conductance calcium-activated potassium channel (BKCa) are the two primary channels for potassium secretion. WNK1 ... In the distal convoluted tubule (DCT), WNK1 is a potent activator of the NCC that results in an increase in sodium re ... GABA activates the GABAA receptor which is a Cl− ion channel. Cl− ions will enter the neuron causing hyperpolarization and ...
... effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels". ...
It may have a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are not appropriate or have ... In addition, moxonidine may also promote sodium excretion, improve insulin resistance and glucose tolerance and protect against ...
... (17-monochloroacetylajmaline) is a drug that is a potent sodium channel blocker (more specifically, a class Ia ... Sodium channel blockers, Secondary alcohols, Carboxylate esters, Indole alkaloids, All stub articles, Cardiovascular system ...
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 ...
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 ...
... Am J Hum Genet. 2001 Jun;68(6): ... Missense mutations in the gene that codes for a neuronal voltage-gated sodium-channel alpha-subunit (SCN1A) were identified in ...
A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC ... Ion channels that specifically allow the passage of SODIUM ions. ... Sodium Ion Channel, Channels, Sodium Ion Expand. Ion channels ... Sodium Channel. Known as: Sodium Channels [Chemical/Ingredient], ... THE CRYSTAL STRUCTURE OF A VOLTAGE-GATED SODIUM CHANNEL. *J. ... Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. *M. Noda, S. Shimizu, +15 authors. S. ...
THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIA ... These results provide a molecular basis for understanding the mechanism of sodium channel modulation through the toxin-channel ... Three-dimensional solution structure of the sodium channel agonist/antagonist delta-conotoxin TxVIA.. Kohno, T., Sasaki, T., ... THREE-DIMENSIONAL STRUCTURE IN SOLUTION OF THE SODIUM CHANNEL AGONIST/ANTAGONIST DELTA-CONOTOXIN TXVIA. *PDB DOI: 10.2210/ ...
... SyncroPatch ... Webinar: "HTS Sodium Ion Channel Assays on the SyncroPatch 384PE". May 08, 2018 ... Whereas NaV1.7 plays a pivotal role in the modulation of action potential threshold, NaV1.8 channel is the predominant channel ... Voltage-gated Na (NaV) channels expressed in dorsal root ganglion neurons (DRG) such as NaV1.7, NaV1.8 and NaV1.9 have been ...
Join this free webinar to learn about how the use of peptide sodium-channel inhibitors derived from venomous organisms can be ... The sodium channel subtype NaV1.7 has been genetically validated to be involved in nociception. Peptide toxins isolated from ... Voltage-gated sodium channels (NaV) are integral in almost all aspects of human physiology, including cardiac and muscle ... Venom Peptides: Rethinking Voltage-Gated Sodium Channel Inhibition. Life Sciences, Drug Discovery & Development, Preclinical, ...
We determined the structures of NaV1.5 DIV S3b-S4a (also known as the paddle motif) from the cardiac sodium channel as well as ... Furthermore, these channels are one of the primary targets of toxins from venomous animals. Animal toxins have been used as an ... will gain more insight into the function of these channels and contribute to rational drug development against these channels. ... Voltage gated sodium channels (VGSC) are membrane proteins that serve an important function in the central nervous system (CNS ...
The epithelial sodium channel (ENaC) is critical in controlling the rate of renal sodium reabsorption and maintaining long term ... Alternative splicing regulation of the epithelial sodium channel (ENaC) in Dahl rats. Description. Title: Alternative splicing ...
Personalized Medicine for Pain with Simon Tate, Convergence Pharma Part 1
Voltage-gated sodium channels (VGSCs) are the target for many therapies. Variation in membrane potential occurs throughout the ... The modulation of voltage-gated sodium channels (VGSCs) and/or Na+,K+-ATPase (sodium pumps) plays a key role in the expression ... Voltage-gated sodium channels and metastatic disease. Channels 6, 352-361 (2012). doi: 10.4161/chan.21910. ... Selective lysis of breast carcinomas by simultaneous stimulation of sodium channels and blockade of sodium pumps. Oncotarget 9 ...
Adaptation to PSTs in other organisms is caused by a mutation in the sodium channel. Recently, a mutation in the sodium channel ... Overall, the results did not support our hypotheses; the mutant sodium channel isoform does not appear to be related to ... Data from: Determining the advantages, costs, and trade-offs of a novel sodium channel mutation in the copepod Acartia ... All A. hudsonica copepods express both the wild-type and mutant sodium channel isoforms, but in different proportions; some ...
You are here: Home / Exposures / Models for the OpenCOR and PMR tutorial by Peter Hunter / sodium_ion_channel.cellml ... sodium_ion_channel.cellml. License and Citation. The terms of use/license for this work is unspecified. Citation Instructions. ...
Epithelial sodium channels (ENaC) are located throughout the epithelial lining of the respiratory tract and play a crucial role ... Subjects with the A663 variant had higher baseline exhaled sodium and a significant decrease in exhaled sodium by 90 minutes ... with the T663 variant resulting in a more active channel due to a greater number of channels in the membrane. We sought to ... Measurements of exhaled sodium were made in the healthy subjects at baseline, 30, 60, and 90 minutes post-albuterol ...
How Batrachotoxin Modifies the Sodium Channel Permeation Pathway: Computer Modeling and Site-Directed Mutagenesis Academic ...
Voltage-gated sodium (Nav) channels are intrinsic plasma membrane proteins that initiate the action potential in electrically ... Namadurai, S., Yereddi, N. R., Cusdin, F. S., Huang, C. L., Chirgadze, D. Y., & Jackson, A. P. (2015). A new look at sodium ... The Nav channels are composed of a pore-forming α subunit and associated β subunits. The β subunits are members of the ... Mutations in Nav channels are implicated in a wide variety of inherited pathologies, including cardiac conduction diseases, ...
Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: A comparison with carbamazepine, ... OXC and LCM on sodium channels endogenously expressed in N1E-115 mouse neuroblastoma cells. CBZ and eslicarbazepine exhibit ... Keywords: Carbamazepine, eslicarbazepine, fast inactivation, lacosamide, oxcarbazepine, slow inactivation, voltage-gated sodium ... Eslicarbazepine- and LCM-treated fast-inactivated channels recovered similarly to control conditions, whereas CBZ- and OXC- ...
Tsuchimochi, H., McCord, J. L., Leal, A. K., & Kaufman, M. P. (2011). Dorsal root tetrodotoxin-resistant sodium channels do not ... Application of the TTX-resistant sodium channel blocker A-803467 (1 μM) with TTX (1 μM) did not block the pressor response to ... Application of the TTX-resistant sodium channel blocker A-803467 (1 μM) with TTX (1 μM) did not block the pressor response to ... Application of the TTX-resistant sodium channel blocker A-803467 (1 μM) with TTX (1 μM) did not block the pressor response to ...
Miller, Victoria (2019) Identification of potent and selective inhibitors of the epithelial sodium channel δ. Doctoral thesis ( ... As such our aim is to identify novel potent and selective inhibitors of the ENaC δ channel which could be used to probe channel ... Identification of potent and selective inhibitors of the epithelial sodium channel δ ... Q Science , QH Natural history , QH0301 Biology , QH0573 Cytology , QH0603.A-Z Other special, A-Z , QH0603.I54 Ion channels. ...
Sodium inward currents through calcium channels in mealworm muscle fibers. In: Archives of Insect Biochemistry and Physiology. ... title = "Sodium inward currents through calcium channels in mealworm muscle fibers",. abstract = "The contribution of Na+ ions ... Yamamoto D. Sodium inward currents through calcium channels in mealworm muscle fibers. Archives of Insect Biochemistry and ... Yamamoto, D 1987, Sodium inward currents through calcium channels in mealworm muscle fibers, Archives of Insect Biochemistry ...
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 ...
... in sodium channel function.. Sodium channel blockers amplify existing INa+ and possibly other ion channel defects, with a ... "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity ... sodium channel pore - how channels open and close. We can also say that it is the process whereby channels change their ... C-terminal tail of the cardiac sodium channel controls channel gating illustrates how subtle changes in channel biophysics can ...
... of a sodium channel called NaV1.7. Sodium channels. transport positively charged sodium atoms (sodium ions) into cells and play ... result in NaV1.7 sodium channels that open more easily than usual and stays open longer than normal, increasing the flow of ... NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. ... Sodium channels in normal and pathological pain. Annu Rev Neurosci. 2010;33:325-47. doi: 10.1146/annurev-neuro-060909-153234. ...
... the sodium channels slowly close and the potassium channels open. Hence the sodium channels are open only momentarily and, now ... To understand this evolutionary quandary we first need a quick review of sodium channels.. What are sodium channels?. Nerve ... In addition to the sodium-potassium pump, there are also sodium channels and potassium channels. These membrane proteins allow ... and then the sodium and potassium channels open and close with precise timing.. Toxic to evolutionary theory. Sodium channels ...
... and sodium-activated potassium channels (KCa, KNa). Detailed annotation on the structure, function, ... BK channel , BK channel alpha subunit , calcium-activated potassium channel alpha subunit , maxi K+ channel , maxi K channel , ... potassium calcium-activated channel subfamily M alpha 1 16. Mouse. 7. 1. 1209. 14 A3. Kcnma1 potassium large conductance ... calcium-activated channel, subfamily M, alpha member 1 Rat. 7. 1. 1209. 15p16. Kcnma1 potassium calcium-activated channel ...
Janiszewski L. The action of toxins on the voltage-gated sodium channel. Pol J Pharmacol Pharm 1990;42:581--8. ... Sodium Azide Clinical Description The majority of exposures to sodium azide occur by inhalation. Signs and symptoms of sodium ... Sodium Monofluoroacetate (Compound 1080) Clinical Description Exposure to sodium monoflouroacetate might cause systemic ... Brevetoxins: unique activators of voltage-sensitive sodium channels. In: Hall S, Strichartz G, eds. Marine toxins. Washington, ...
... Academic Article ... The mechanosensitivity of the epithelial sodium channel (ENaC) is controversial. Using cell-attached patch-clamp techniques, we ...
Mutations in the neuronal sodium voltage-gated channel, alpha subunit 1 (SCN1A) gene have been associated with epilepsy. We ... SCN1A encodes the alpha subunit of the sodium channel NaV1.1 [7]. This type of channels conduct sodium ions through pores in ... polymorphism has been suggested to be involved in the gating of sodium channels, thus rendering them insensitive to sodium- ... lacosamide and lidocaine prevent seizure activity through blocking the movement of sodium ions across sodium ion channels ...
ion channel, POTASSIUM CHANNEL, inward rectification, sodium binding, PIP2 binding, G protein binding, METAL TRANSPORT ... Crystal structure of the G protein-gated inward rectifier K+ channel GIRK2 (Kir3.2) in complex with sodium and PIP2. ... Crystal Structure of the Mammalian GIRK2 K(+) Channel and Gating Regulation by G Proteins, PIP(2), and Sodium. ...
  • Ion channels that specifically allow the passage of SODIUM ions. (
  • The opening of VGSCs that allows for the entry of sodium into the cell and depolarization of the cell membrane is required for transition from G0 to G1 [15] The sodium pump returns sodium ions to the extracellular space and restores the resting membrane potential and the intracellular sodium concentration. (
  • transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. (
  • result in NaV1.7 sodium channels that open more easily than usual and stays open longer than normal, increasing the flow of sodium ions into nociceptors. (
  • This increase in sodium ions enhances transmission of pain signals, leading to the signs and symptoms of erythromelalgia. (
  • First, there is a membrane protein that simultaneously pumps potassium ions into the cell and sodium ions out of the cell. (
  • Sodium ions outside the cell then come streaming into the cell down the electro-chemical gradient. (
  • Hence the sodium channels are open only momentarily and, now with the potassium channels open, the potassium ions concentrated inside the cell come streaming out down their electro-chemical gradient. (
  • This occurs through affection of the membrane permeability to sodium ions and facilitation of the ions diffusion down an electrochemical gradient till the sodium equilibrium potential [ 3 ]. (
  • This type of channels conduct sodium ions through pores in the cellular membranes. (
  • Carbamazepine, oxcarbazepine, phenytoin, lamotrigine, lacosamide and lidocaine prevent seizure activity through blocking the movement of sodium ions across sodium ion channels during the propagation of action potentials. (
  • Sodium channels are highly selective for the transport of ions across cell membranes. (
  • Flow of ions through voltage gated channels can be represented theoretically using stochastic differential equations where the gating mechanism is represented by a Markov model. (
  • When ligands bind to the receptor, the ion channel portion of the receptor opens, allowing ions to pass across the cell membrane . (
  • If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. (
  • Many LICs are additionally modulated by allosteric ligands , by channel blockers , ions , or the membrane potential . (
  • When the acetylcholine binds it alters the receptor's configuration (twists the T2 helices which moves the leucine residues, which block the pore, out of the channel pathway) and causes the constriction in the pore of approximately 3 angstroms to widen to approximately 8 angstroms so that ions can pass through. (
  • With a sufficient number of channels opening at once, the inward flow of positive charges carried by Na + ions depolarizes the postsynaptic membrane sufficiently to initiate an action potential . (
  • Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na + ) through a cell's plasma membrane. (
  • Starting from native material or recombinant systems, we succeed with all types of membrane proteins: GPCRs, Ions Channels, Transporters, Receptors and Viral Proteins. (
  • Missense mutations in the gene that codes for a neuronal voltage-gated sodium-channel alpha-subunit (SCN1A) were identified in families with generalized epilepsy with febrile seizures plus (GEFS+). (
  • The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. (
  • Mutations in the neuronal sodium voltage-gated channel, alpha subunit 1 ( SCN1A) gene have been associated with epilepsy. (
  • Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (
  • These minor changes are found in segments of the sodium channel gene which otherwise is highly conserved across a wide range of species. (
  • To identify the molecular mechanisms underlying pyrethroid resistance in S. zeamais, the domain II region of the voltage-gated sodium channel (para-orthologue) gene was amplified by PCR and sequenced from susceptible and resistant laboratory S. zeamais strains that were selected with a discriminating dose of DDT. (
  • Genetic elements involved in cell-specific expression of the type II sodium channel gene were revealed using transient expression assays. (
  • A chimeric reporter gene containing 1051 by of the sodium channel 5′ flanking region was active in neuroblastoma and PC12 cells, but inactive in nonneuronal cell types. (
  • This gene belongs to the amiloride-sensitive Na+ channel and degenerin (NaC/DEG) family, members of which have been identified in many animal species ranging from the nematode to human. (
  • The amiloride-sensitive Na(+) channel encoded by this gene is primarily expressed in the small intestine, however, its exact function is not known. (
  • The majority of resistance-associated mutations are found in segment 6 of domain II (IIS6) and domain III (IIIS6) of the sodium channel gene. (
  • This gene encodes one of the many voltage-gated sodium channel proteins. (
  • Using insecticides to (IIIS6) of the sodium channel gene. (
  • The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells. (
  • Whereas Na V 1.7 plays a pivotal role in the modulation of action potential threshold, Na V 1.8 channel is the predominant channel driving and shaping TTX-resistant action potentials (AP) in DRG neurons. (
  • Although Na V 1.9 probably does not contribute to action potential amplitude, it most likely acts as a threshold channel, contributing to resting membrane potential and lowering the threshold for action potentials thereby increasing repetitive firing 4 . (
  • Neuronal voltage-gated sodium channels (SCN) are proteins responsible for the generation and propagation of the action potentials within the neurons. (
  • For proper functioning of neurons and muscles during action potentials, voltage-gated sodium channels direct sodium ion diffusion for membrane depolarization. (
  • They modulate multiple aspects of Nav channel behaviour and play critical roles in controlling neuronal excitability. (
  • Diversos subtipos específicos de canales de sodio están implicados en funciones especializadas como la señalización neuronal, la contracción del MÚSCULO CARDÍACO y la función del RIÑÓN. (
  • A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function. (
  • Voltage-gated K+ channels are important determinants of neuronal membrane excitability (Pongs, 1999). (
  • Moreover, differences in K+ channel expression patterns and densities contribute to the variations in action potential waveforms and repetitive firing patterns evident in different neuronal cell types. (
  • The delayed rectifier-type (IK)channels (Kv1.5, Kv2.1, and Kv2.2) are expressed on all neuronal somata and proximal dendrites and are also found in a wide variety of non-neuronal cells types including pancreatic islets, alveolar cells and cardiac myocytes (Hwang et al. (
  • The precise mechanism is unknown, but it has been shown to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. (
  • Mutations in Nav channels are implicated in a wide variety of inherited pathologies, including cardiac conduction diseases, myotonic conditions, epilepsy and chronic pain syndromes. (
  • SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels. (
  • This group of antiepileptic drugs (AEDs) has an additional advantage through acting on potassium channels, due to structural similarities, thus controlling genetic epilepsies due to mutations of voltage-gated potassium channel genes [ 9 ]. (
  • Interestingly, mutations in the human cardiac sodium channel are known to lead to cardiac abnormalities, which result in arrhythmias and frequently in sudden cardiac death. (
  • The authors highlight the implication that mutations in this channel known to cause arrhythmia could also cause epilepsy. (
  • Knockdown resistance (kdr) is a mechanism that describes cases of resistance to pyrethroid as a result of target site insensitivity due to point mutations in the insect voltage-gated sodium channel (VGSC) regulatory protein, which block pyrethroid and DDT action (genetic makeup) (4). (
  • have been reported describes cases of resistance to pyrethroid as a result of from Singapore ( 11 ), China ( 12,13 ) and Greece ( 13 ), and target site insensitivity due to point mutations in the 1534Leu and 1534Ser have been found in the United States insect voltage-gated sodium channel (VGSC) regulatory of America ( 14 ). (
  • Mutations for mammoth hemoglobin, extra hair growth, fat production, down to nuanced climate adaptations such as slightly altered sodium ion channels in cell membranes have already been engineered into fibroblast cell lines. (
  • Voltage gated sodium channels (VGSC) are membrane proteins that serve an important function in the central nervous system (CNS), peripheral nervous system (PNS), and cardiac muscles amongst others. (
  • Voltage-gated sodium (Nav) channels are intrinsic plasma membrane proteins that initiate the action potential in electrically excitable cells. (
  • These membrane proteins allow sodium and potassium, respectively, to pass through the membrane. (
  • Crystal Structure of the Mammalian GIRK2 K(+) Channel and Gating Regulation by G Proteins, PIP(2), and Sodium. (
  • This domain is found in sodium, potassium, and calcium ion channels proteins. (
  • In some Na channel proteins the domain is repeated four times, whereas in others (e.g. (
  • Like many membrane proteins, the ion channel TRPC5 has no surface-exposed termini. (
  • the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. (
  • domain 4 has fewer arginine and lysine residues compared to other sodium channel proteins. (
  • CALIXAR's approach allows to preserve the original structure and function of membrane proteins (GPCRs, Ion Channels, Transporters, Receptors, Anchors and Viral Proteins) providing solutions for pharmaceutical industries, biotechnology companies and academic teams to develop conformational antibodies, formulate new vaccines, carry out Structure Based Drug Discovery and/or HTS assays. (
  • We discovered that absence of all seven TRPC proteins in mice (TRPC HeptaKO mice) promotes the development of dextran sulfate sodium (DSS)-induced colitis. (
  • 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). (
  • They function to inhibit Na V activity by blocking the pore domain (pore blockers) or by binding to the membrane-embedded voltage sensor domain of the sodium channel (gating-modifier toxins). (
  • Other channel blockers include: charybdotoxin, iberiotoxin and tetraethylammonium. (
  • Several studies have reported the efficacy of the sodium-channel blockers for the treatment of epilepsies due to genetic channelopathies. (
  • The use of beta-blockers or nondihydropyridine calcium channel blockers (CCBs) is appropriate. (
  • Calcium channel blockers and beta blockers are poor choices because they will exacerbate hypotension. (
  • Yamamoto, D 1987, ' Sodium inward currents through calcium channels in mealworm muscle fibers ', Archives of Insect Biochemistry and Physiology , vol. 5, no. 4, pp. 227-231. (
  • AIM OF THE STUDY: The effects of GA on the cardiac sodium currents (I(Na)), L-type calcium currents (I(Ca,L)) and hyperpolarization-activated inward currents (I(f)) were investigated. (
  • MATERIALS AND METHODS: Human isoforms of wild-type and DeltaKPQ-mutant type sodium channels were expressed in Xenopus oocytes, and the resulting currents (peak and late I(Na)) were recorded using a two-microelectrode voltage-clamp technique. (
  • CONCLUSION: GA blocked cardiac sodium currents, particularly late I(Na. (
  • Our findings might help to understand the traditional use of licorice in the treatment of cardiovascular disorders, because reduction of sodium currents (particularly late I(Na)) would be expected to provide protection from Na(+)-induced Ca(2+) overload and cell damage. (
  • Despite extensive expression attempts, currents from the putative channel were not detected. (
  • In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. (
  • Ample data support a prominent role of peripheral T-type calcium channels 3.2 (Ca V 3.2) in generating pain states. (
  • Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels. (
  • Hint: Your Response should directly apply to Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels. . (
  • Predicting functional effects of missense variants in voltage-gated sodium and calcium channels. (
  • In addition, our data strengthen the hypothesis that nonselective calcium channels are involved in aminoglycoside uptake. (
  • The epithelial sodium channel (ENaC) is critical in controlling the rate of renal sodium reabsorption and maintaining long term blood pressure control. (
  • Epithelial sodium channels (ENaC) are located throughout the epithelial lining of the respiratory tract and play a crucial role in ion and fluid homeostasis of the lungs. (
  • Increasing ENaC activity through stimulation of β₂-adrenergic receptors has been shown to increase sodium and fluid reabsorption from the airspace to the interstitial space. (
  • In cystic fibrosis lung disease there is a hyperabsorption of sodium through ENaC which results in dehydration of the airway surface liquid. (
  • More specifically the neuronally-expressed ENaC δ channel has been linked to the integration of ischemia- related signals in inflamed and hypoxic tissues (Ji, et al. (
  • As such our aim is to identify novel potent and selective inhibitors of the ENaC δ channel which could be used to probe channel function. (
  • A heterologous expression system was developed to overexpress the ENaC δβγ channel in a Human Embryonic Kidney (HEK) 293 cell line. (
  • This implemented a BacMam baculoviral delivery system to transiently express ENaC δ subunit in HEK293 cell which stably expressed ENaC β and γ subunits, reconstituting channel function. (
  • This expression system has been used to establish both a novel membrane potential-based fluorescence assay and an automated electrophysiological-based assay to screen for regulators of ENaC δ channel function. (
  • This has been used to support an SAR-based approach to improve potency and selectivity in the development of a tool compound to investigate the ENaC δβγ channel. (
  • The mechanosensitivity of the epithelial sodium channel (ENaC) is controversial. (
  • In these cells, both ENaC and the water channel aquaporin AQP9 are localized on these projections and also in the basal and smooth muscle layers [ 13 ]. (
  • Epithelial Na+ channels, or ENaCs, belong to the (ENaC)/degenerin family, and their extracellular domains interact with ohter factors that regulate channel gating. (
  • The degenerin/epithelial sodium channel (DEG/ENaC) superfamily of ion channels contains subfamilies with diverse functions that are fundamental to many physiological and pathological processes, ranging from synaptic transmission to epileptogenesis. (
  • We recently reported that the nonproton agonist 2-guanidine-4-methylquinazoline (GMQ) activates acid-sensing ion channels (ASICs), a DEG/ENaC subfamily mainly in mammals, in the absence of acidosis. (
  • 2015), ' Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons. . (
  • Sodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus. (
  • We report the cloning of a novel protein that contains the four domain structure found in voltage-gated Ca2+ and Na+ channels. (
  • Phylogenetic relationships suggested that the protein might have diverged from an ancestral four repeat channel before the divergence of Ca2+ and Na+ channels. (
  • Based on its sequence, we propose that the novel protein might be a voltage-activated cation channel with unique gating properties. (
  • K channels) the protein forms a tetramer in the membrane. (
  • The mechanisms of benefit involve alkalinization to override the TCA s myocardial sodium channel blockade and boost protein binding so the drug doesn t cause additional problems, along with an increase in the extracellular sodium channel concentration to improve the cross-channel gradient. (
  • ABSTRACT: Cloning has led to the discovery of more ion channels than predicted by functional studies, yet there remain channels that have not been cloned. (
  • By solving the structural details of the interaction between animal toxins and VGSC we will gain more insight into the function of these channels and contribute to rational drug development against these channels. (
  • This study aimed at evaluating the effects of eslicarbazepine, carbamazepine (CBZ), oxcarbazepine (OXC) and lacosamide (LCM) on the fast and slow inactivated states of voltage-gatedsodium channels (VGSC). (
  • Peptide toxins isolated from venomous creatures are potent inhibitors of human voltage-gated sodium channels, with venom peptides selective against Na V 1.7 showing great potential as therapeutic pain relief agents. (
  • Development of primary sensory neuron-specific inhibitors of Ca V 3.2 channels is an opportunity for achieving effective analgesic therapeutics, but success has been elusive. (
  • Voltage-gated Na (Na V ) channels expressed in dorsal root ganglion neurons (DRG) such as Na V 1.7, Na V 1.8 and Na V 1.9 have been proposed to play important roles in nociception and pain signalling 1 . (
  • Voltage-gated sodium channels (Na V ) are integral in almost all aspects of human physiology, including cardiac and muscle function and pain perception. (
  • In this webinar, delineating the mechanism of action behind venom peptide inhibition of voltage-gated sodium channels will be presented. (
  • Voltage-gated sodium channels (VGSCs) are the target for many therapies. (
  • As a result the voltage drop is reversed and the decaying electronic impulse, which caused the sodium channels to open, is boosted as it continues on its way along the nerve cell tail. (
  • When the voltage goes from negative to positive inside the cell, the sodium channels slowly close and the potassium channels open. (
  • The intensive use of compounds such as the pyrethroids has led to the emergence of resistance, and previous studies have suggested that resistance to both pyrethroids and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) may result from reduced sensitivity of the insecticide target, the voltage-gated sodium channel. (
  • Janiszewski L. The action of toxins on the voltage-gated sodium channel. (
  • Expression of the rat (RH-I/SkM2) and human (hH1/SCN5A) tetrodotoxin-resistant (TTX-R), voltage-sensitive sodium channels is thought to be specific to cardiac tissue. (
  • Identifies presence of mRNA for tetrodotoxin-resistant voltage-sensitive sodium channel, previously believed present only in heart, in fetal and adult brain. (
  • Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. (
  • Voltage-gated sodium channels are targets for many analgesic and antiepileptic drugs whose therapeutic mechanisms and binding sites have been well-characterized. (
  • This flavanone named as pinostrobin helps to inhibit voltage - gated sodium channels. (
  • 2011. Thiazolidinedione insulin sensitizers alter lipid bilayer properties and voltage-dependent sodium channel function: implications for drug discovery. . (
  • The pressor responses to static contraction, to tendon stretch, and to electrical stimulation of the tibial nerve were compared before and after blocking TTX-sensitive sodium channels on the L3-L6 dorsal roots of rats whose hindlimbs were freely perfused and rats whose femoral arteries were ligated 72 h before the start of the experiment. (
  • Although the contribution of TTX-resistant sodium channels to the augmented exercise pressor reflex may be slightly increased in rats with chronic femoral artery ligation, TTX-resistant sodium channels on dorsal roots do not play a major role in the augmented exercise pressor reflex. (
  • The left flipper (LF) domain of the P2X receptors is a flexible loop structure, and its coordinated motions together with the dorsal fin (DF) domain are crucial for the channel gating of the P2X receptors. (
  • These compounds inhibit sodium channels and prevent sodium conductance by delaying channel recovery from the inactivated state. (
  • 2014. Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer properties. . (
  • After sodium chloride is dissolved in snow, its freezing point is -10? (
  • The global De-icing Sodium Chloride market was valued at US$ million in 2022 and is anticipated to reach US$ million by 2029, witnessing a CAGR of % during the forecast period 2023-2029. (
  • North American market for De-icing Sodium Chloride is estimated to increase from $ million in 2023 to reach $ million by 2029, at a CAGR of % during the forecast period of 2023 through 2029. (
  • This report aims to provide a comprehensive presentation of the global market for De-icing Sodium Chloride, with both quantitative and qualitative analysis, to help readers develop business/growth strategies, assess the market competitive situation, analyze their position in the current marketplace, and make informed business decisions regarding De-icing Sodium Chloride. (
  • The De-icing Sodium Chloride market size, estimations, and forecasts are provided in terms of output/shipments (K MT) and revenue ($ millions), considering 2022 as the base year, with history and forecast data for the period from 2018 to 2029. (
  • This report segments the global De-icing Sodium Chloride market comprehensively. (
  • The report will help the De-icing Sodium Chloride manufacturers, new entrants, and industry chain related companies in this market with information on the revenues, production, and average price for the overall market and the sub-segments across the different segments, by company, by type, by application, and by regions. (
  • Chapter 2: Detailed analysis of De-icing Sodium Chloride manufacturers competitive landscape, price, production and value market share, latest development plan, merger, and acquisition information, etc. (
  • Chapter 3: Production/output, value of De-icing Sodium Chloride by region/country. (
  • Chapter 4: Consumption of De-icing Sodium Chloride in regional level and country level. (
  • We have known for decades that ion channels and shifts in membrane potential play important roles in the cell cycle that are responsible for preparing the cell for the sequence of events that must take place to ensure maintenance, replication and survival, through control of constantly changing intra- and extracellular ion concentrations [15]. (
  • Although the extracellular ATP-gated cation channel purinergic receptor P2X5 is widely expressed in heart, skeletal muscle, and immune and nervous systems in mammals, little is known about its functions and channel-gating activities. (
  • We determined the structures of Na V 1.5 DIV S3b-S4a (also known as the paddle motif) from the cardiac sodium channel as well as that of a sea anemone toxin Anthopleurin A (ApA) known to bind that region of the channel by Nuclear Magnetic Resonance (NMR) spectroscopy in dodecylphosphocholine (DPC) micelles. (
  • Donahue LM, Coates PW, Lee VH, Ippensen DC, Arze SE, and Poduslo SE (2000) The cardiac sodium channel mRNA is expressed in the developing and adult rat and human brain. (
  • NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. (
  • These amiloride analogues all exhibit activity at multiple ion channels and have poor pharmacokinetic properties with respect to CNS penetration. (
  • Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na(+) channel from human small intestine. (
  • Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (
  • The role of sodium channels in injury-induced trigeminal pain. (
  • A new look at sodium channel β subunits. (
  • The Nav channels are composed of a pore-forming α subunit and associated β subunits. (
  • In particular, the discovery that β3 subunits form trimers suggests that Nav channel oligomerization may contribute to the functional properties of some β subunits. (
  • These channels influence such functions as blood pressure and vascular smooth muscle and are composed of three subunits: alpha, beta and gamma. (
  • This will include discussion on engineering peptides to achieve subtype specificity and complete inhibition of specific sodium channels to unlock the potential of potent venom peptides as therapeutic leads for the treatment of pain. (
  • Bulk Order Inquiry for Anti-Kv2.2 Potassium Channel Antibody ------- (please add any order requirements, including desired quantity, timing, etc. (
  • For example, during the G1/S transition, the membrane potential is hyperpolarized due to influx of sodium and efflux of potassium [15]. (
  • Gating current (Ig) has been studied in relation to inactivation of Na channels. (
  • However, the mechanism underlying the crucial role of the LF domain in the channel gating remains obscure. (
  • 2011. PIP2-mediated HCN3 channel gating is crucial for rhythmic burst firing in thalamic intergeniculate leaflet neurons. . (
  • The inelastic scattering of positrons by excited lithium alkali atoms Li * (2p) have been investigated within the frame work of the coupled-static and frozen-core approximations with the assumption that the elastic and rearrangement channels are open. (
  • Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. (
  • The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor . (
  • Tamoxifen, an estrogen receptor modulator, and its metabolites bind at the intracellular exit of the channel, which is different from other previously characterized drug sites. (
  • The transient receptor potential canonical (TRPC) channels, encoded in seven non-allelic genes, are important contributors to calcium fluxes, are strongly associated with various diseases. (
  • Serum samples (0.2 mL) were diluted with 1.2 mL of 50mM potassium tetraborate in 1% sodium ascorbate and vortexed. (
  • Application of the TTX-resistant sodium channel blocker A-803467 (1 μM) with TTX (1 μM) did not block the pressor response to tibial nerve stimulation to any greater extent than did application of TTX (1 μM) alone. (
  • They are normally closed, but when the electronic impulse travels along the nerve cell tail, it causes the sodium channels to quickly open. (
  • Finding aqueous pores in sodium channels. (
  • Furthermore, these channels are one of the primary targets of toxins from venomous animals. (
  • In this study, we tested whether TRPC nonselective cation channels contribute to the variable PTC readthrough effect of aminoglycosides by controlling their cellular uptake. (
  • We also show that AC1903 inhibited TRPV4 channels, but had weak or no effects on TRPV1 and no effect on the nonselective cation channel PIEZO1. (
  • The three-dimensional solution structure of delta-conotoxin TxVIA, a 27-mer peptide agonist/antagonist of sodium channels, was determined by two-dimensional (1)H NMR spectroscopy with simulated annealing calculations. (
  • The absence in mammals of some DEG/ENaCs subfamily orthologues such as FMRFamide peptide-activated sodium channels (FaNaCs), which have been identified only in mollusks, indicates that the various subfamilies diverged early in evolution. (
  • Many structures and processes are involved in the development of a seizure, including neurons, ion channels, receptors, glia, and inhibitory and excitatory synapses. (
  • To study the mechanisms through which these neurons integrate complex input patterns, a new set of models were developed using the latest experimental information and a genetic algorithm approach to fit the maximum ionic channel conductances. (
  • These results provide a molecular basis for understanding the mechanism of sodium channel modulation through the toxin-channel interaction and insight into the discrimination of different ion channels. (
  • Adaptation to PSTs in other organisms is caused by a mutation in the sodium channel. (
  • Recently, a mutation in the sodium channel in A. hudsonica was found. (
  • From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. (
  • We investigated the contribution of tetrodotoxin (TTX)-resistant sodium channels to the augmented exercise pressor reflex observed in decerebrated rats with femoral artery ligation. (
  • Sodium channels are a great target for a biological toxin such as tetrodotoxin. (
  • Tetrodotoxin wreaks its havoc by binding to the opening of the sodium channel. (
  • But for all its lethality, tetrodotoxin can be neutralized with merely a few changes to the sodium channel's amino acid string. (
  • The fourth quarter of 2022 saw a decline in market sentiment for Sodium Benzoate in North America because of poor offtakes in downstream industries such as the production of food and drink and pharmaceuticals. (
  • Prices for Sodium Benzoate were estimated in December to be around USD 1650/MT for Sodium Benzoate for CFR New York towards the end of the fourth quarter of 2022. (
  • The Asia Pacific Sodium Benzoate market showed a decline in market sentiments in the fourth quarter of 2022. (
  • Throughout the fourth quarter of 2022, the European market for Sodium Benzoate continued to decline. (
  • The Asia Pacific Sodium Benzoate market showed varying market sentiments in the third quarter of 2022. (
  • Towards the end of the Q3 of 2022, the prices for Sodium Benzoate were assessed at around USD 2170/MT for FOB Shanghai in September. (
  • In September, the cost of Sodium Benzoate for CFR Hamburg was estimated to be around USD 3175/MT toward the end of Q3 of 2022. (
  • Significant progress has been made in understanding the roles of crucial residues/motifs in the channel function of P2X receptors during the pre-structure era. (
  • During the G2/M transition, the activity of potassium channels is decreased, leading to a decrease in intracellular potassium, resulting in hyperpolarization [15, 17]. (
  • A molecular docking study revealed that the rac-5c analog showed higher affinities than propafenone in relation to beta 1 and beta 2 adrenergic receptors, as well as sodium channels. (
  • If these mutant channels were also expressed in limbic regions of the brain, alterations in channel function could have drastic effects on the brain's signaling ability, possibly promoting seizure activity. (
  • Blockade of cardiac fast sodium channels (leads to wide QRS, R-wave in aVR, R' wave in V1, Brugada pattern ECG, ventricular dysrhythmias. (
  • The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species. (
  • Glycyrretinic acid blocks cardiac sodium channels expressed in Xenopus oocytes. (
  • Indeed, in our experiments, AC1903 inhibited multiple TRPC channels including TRPC3, TRPC4, TRPC5, TRPC6, TRPC4-C1, and TRPC5-C1, as well as endogenous TRPC1:C4 channels in A498 renal cancer cells, all with low micromolar IC50 values (1.8-18 µM). (
  • 2013. HCN1 channels as targets for anesthetic and nonanesthetic propofol analogs in the amelioration of mechanical and thermal hyperalgesia in a mouse model of neuropathic pain. . (
  • In the CF patients we predicted that the T663 variant would be detrimental to lung function due to an exaggerated absorption of sodium and drying/thickening of the mucus layer in the airways. (
  • Introduce a compound that clogs the channel and nerves and muscles lose function. (
  • Tabb , JS et al "Suppression of sodium channel function in differentiating C2 muscle cells stably overexpressing rat androgen receptors. (
  • Some antiepileptic drugs work by acting on combination of channels or through some unknown mechanism of action. (