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.
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.
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 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 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 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.
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 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.
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 in neuronal tissue that mediates the sodium ion PERMEABILITY of excitable membranes.
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.
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.
A class of drugs that stimulate sodium influx through cell membrane channels.
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 study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
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.
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.
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.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
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.
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.
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
The ability of a substrate to allow the passage of ELECTRONS.
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.
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).
A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.
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.
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.
The rate dynamics in chemical or physical systems.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
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 benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.
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.
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.
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 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.
Established cell cultures that have the potential to propagate indefinitely.
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 chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)
A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.
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)
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
A 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.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
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.
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 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 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.
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.
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.
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.
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 delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
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.
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.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A voltage-gated sodium channel beta subunit that binds covalently to voltage-gated alpha subunits.
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.
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 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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.
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.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
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 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.
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 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 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.
Proteins prepared by recombinant DNA technology.
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.
Elements of limited time intervals, contributing to particular results or situations.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.
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.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
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)
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
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.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
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)
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
Use of electric potential or currents to elicit biological responses.
Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION CHANNELS.
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
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.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
A ubiquitous sodium salt that is commonly used to season food.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
A voltage-gated potassium channel that is expressed primarily in the HEART.
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.
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.
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 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.
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.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
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.
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.
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.
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.
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.
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.
Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.
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.
The physical characteristics and processes of biological systems.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
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.
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.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
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.
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
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.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The hollow, muscular organ that maintains the circulation of the blood.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
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.
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)
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.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
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 shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
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.
Proteins obtained from species in the class of AMPHIBIANS.
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 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.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
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.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
Transport proteins that carry specific substances in the blood or across cell membranes.
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 mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
Contractile tissue that produces movement in animals.
Organic salts or esters of methanesulfonic acid.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
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 variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.
A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.
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.
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 phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
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.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
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)
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.
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.
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.
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.
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.
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.
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.
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.
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 genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
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.
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.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
The order Actiniaria, in the class ANTHOZOA, comprised of large, solitary polyps. All species are carnivorous.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
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 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.
Proteins found in any species of bacterium.
Additionally, grayanotoxin only binds to the activated conformation of sodium channels. Normally, voltage gated sodium channels ... The Nav1.x channels consist of four homologous domains (I-IV), each containing six transmembrane alpha-helical segments (S1-S6 ... At the peak of the action potential, voltage-gated sodium channels are quickly inactivated and are only reset once the cell has ... The toxicity of grayanotoxin is derived from its ability to interfere with voltage-gated sodium channels located in the cell ...
Additionally, grayanotoxin only binds to the activated conformation of sodium channels. Normally, voltage gated sodium channels ... The Nav1.x channels consist of four homologous domains (I-IV), each containing six transmembrane alpha-helical segments (S1-S6 ... At the peak of the action potential, voltage-gated sodium channels are quickly inactivated and are only reset once the cell has ... The toxicity of grayanotoxin is derived from its ability to interfere with voltage-gated sodium channels located in the cell ...
Carvacrol inhibits the neuronal voltage-gated sodium channels Nav1. .2, Nav1. .6, Nav1. .3, Nav1. .7, and Nav1. .8 expressed in ... Residues in Transmembrane Segments of the P2X4. Receptor Contribute to Channel Function and Ethanol Sensitivity., Popova M., ... A doublecortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin ... Association of A Novel Splice Site Mutation in P/Q-Type Calcium Channels with Childhood Epilepsy and Late-Onset Slowly ...
CK2 was further found to directly phosphorylate the voltage gated sodium channel NAv1, thereby enhancing its binding to ankyrin ... a transmembrane protein involved in the synaptic vesicle fusion with the presynaptic membrane [53], syntaxin, a synaptotagmin ... CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability. FASEB J. ... Another family of membrane proteins that modulate synaptic activity are the voltage gated sodium channels (NAvs). Recently, the ...
SCN2A is a voltage-gated sodium channel expressed widely on neurons. We considered this mutation as likely pathogenic as Leu248 ... Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5-UFM1 Complex. Cell Rep 2016;16:3113-20.doi: ... The surrounding peptide sequence NLILAVVAMA is conserved in all human Nav1.n proteins (except Nav1.9-where it is NLTLAVVAMA, in ... This apparently trivial change occurs in the intracellular portion of the domain I-S6 transmembrane domain. This is a critical ...
... voltage-gated sodium channels (Nav) or neurofascin-186) led to a decrease of ankG concentration and perturbed the AIS formation ... effects were rescued by expressing a recombinant AIS-targeted Nav or by a minimal construct containing the ankyrin-binding ... voltage-gated sodium channels (Nav) or neurofascin-186) led to a decrease of ankG concentration and perturbed the AIS formation ... effects were rescued by expressing a recombinant AIS-targeted Nav or by a minimal construct containing the ankyrin-binding ...
sodium channel complex. GO:0034706 9.43. SCN2A SCN1B SCN1A 12. voltage-gated sodium channel complex. GO:0001518 9.17. SCN9A ... transmembrane transport. GO:0055085 10.03. SCN9A SCN8A SCN7A SCN3A SCN2A SCN1A 3. ion transmembrane transport. GO:0034220 10.01 ... voltage-gated sodium channel activity. GO:0005248 9.23. SCN9A SCN8A SCN7A SCN3A SCN2A SCN1B ... Sodium Voltage-Gated Channel Beta Subunit 1. Protein Coding. 800.39. Pathogenic/Likely pathogenic 6 ...
Intro gene encodes the -subunit of cardiac voltage-gated Na+ channels (Nav1.5), which generate the inward sodium current (INa) ... Introduction We functionally analyzed a frameshift mutation in the gene encoding cardiac Na+ channels (Nav1. that was not ... particularly the PDZ binding website, which, in turn, are critical for channel trafficking and surface manifestation. A huge ... amount of disease-causing mutations have been recognized in transmembrane segments of Nav1.5. However, mutations in the C- ...
... including the voltage-gated sodium channel (Nav1) β2 subunit, Golgi-localized membrane-bound α2,6-sialyltransferase, P-selectin ... PSs are multi-transmembrane proteins with an unclear number of transmembrane domains [104]. Nascent PSs undergo ... and had subtle electrophysiological alterations in the steady-state inactivation of their voltage-gated sodium channels. They ... through its transmembrane domain [114, 115]. However, another study failed to confirm the binding of TMP23/p21 to γ-secretase, ...
Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. Many of ... Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors ... Actions of sea anemone type 1 neurotoxins on voltage-gated sodium channel isoforms. Toxicon 2009, 54, 1102-1111. [Google ... The analysis of neurotoxin (Nav1) evolution exposed extensive genomic expansion of this region [42]. Gene expansion has shaped ...
µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ... In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the ... Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and ... Mahdavi, S.; Kuyucak, S. Molecular dynamics study of binding of µ-conotoxin GIIIA to the voltage-gated sodium channel Nav1. 4. ...
... ... Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs: Insights from Cellular Trafficking. ... CRF-binding protein, and two receptors - CRF type 1 and CRF type 2. This review summarizes how acute, binge, and chronic ... Voltage-gated sodium channel (VGSC) beta (β) subunits have been called the overachieving auxiliary ion channel subunit. ...
... review will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels ... review will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels ... molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels. ... We will also discuss the relevance of proper ion channel targeting for neuronal physiology and how alterations in polarized ...
transient receptor potential a cation channel with 30 transmembrane domains voltage gated sodium channel voltage gated calcium ... noted that many pain syndromes are due to defect in activity of Nav1 type channels caused by mutations in sodium channel genes ... Rhodopsin is a protein that binds to 11-cis retinal, it is activated by light, Rhodopsin is essential for vision in dim light. ... Voltage-gated sodium channels: (NaV)igating the field to determine their contribution to visceral nociception. J Physiol 2018; ...
Loss-of-function mutations in the gene encoding voltage-gated sodium route Nav1. Nav1.7-null January 21, 2019. Published by: ... whereas the 4-subunit of voltage-gated calcium mineral channels has been proven to truly have a part like a transcription ... We tested the consequences of IL-1RA in conjunction with non-Fc receptor (FcR) binding anti-CD3 mAb, which includes been proven ... provided associated with the chosen transmembrane transporters in the OATP, OAT, SLC51, and ABC-transporter households, as well ...
Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje ... Ankyrin-binding proteins related to nervous system cell adhesion molecules: candidates to provide transmembrane and ... AnkG is required for AIS formation. (A) 10-DIV hippocampal neurons transfected with Nav channel shRNA (Nav1.x shRNA), ankG ... voltage-gated Na+ [Nav]) channels at axon initial segments (AIS) and nodes of Ranvier. In addition to ion channels, these ...
... ... voltage sensing, gating, and inactivation, in one central, polytopic, transmembrane protein... ... ... Voltage-gated sodium channels belong to the superfamily of voltage-gated cation channels. Their structure is based on domains ...
sodium channel complex. GO:0034706 9.5. SCN2A SCN1B SCN1A 12. voltage-gated sodium channel complex. GO:0001518 9.4. SCN9A SCN8A ... ion channel binding. GO:0044325 9.76. SCN5A SCN4B SCN1B SCN10A 6. calcium channel activity. GO:0005262 9.67. TRPV1 TRPA1 ... transmembrane transport. GO:0055085 10.22. TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4A 2. ion transmembrane transport. GO:0034220 10.13 ... SCN8A SCN1A NAV1 9. node of Ranvier. GO:0033268 9.56. SCN8A SCN2A SCN1B SCN1A ...
... and Nav1.6/SCN8A and shows higher affinity for insect Nav1/para channels (site 3). Induces tonic repetitive firing of nerve ... Selectively slows channel inactivation of mammalian Nav1.1/SCN1A, Nav1.3/SCN3A, ... Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin. ... of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel.". ...
A homozygous mutation of voltage-gated sodium channel β I gene SCN1B in a patient with Dravet syndrome: Homozygous SCN1B ... Identification of a new co-factor, mog1, required for the full function of cardiac sodium channel nav1. 5. Journal of ... the ATP-binding cassette transporter for the KATP channel) mutations affected the ATP-sensitive potassium channel (or KATP ... Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by ...
Background The Nav1.7 subtype of voltage-gated sodium channels is specifically expressed in sensory and sympathetic ganglia ... The radioligand binding to the cells heterologously expressing GluA1 and/or γ-8 revealed that γ-8 TDAAs binds to γ-8 alone ... Gene expression analysis showed that that NaV 1.7 was virtually the only tetrodotoxin-sensitive NaV1 gene expressed in guinea ... transmembrane AMPA receptor regulatory protein (TARP) γ8, which is highly expressed in the hippocampus but also in pain ...
Voltage-gated Na(+) (Na(V)) channels initiate neuronal action potentials. Na(V) channels are composed of a transmembrane domain ... Categories: Human , Chung, B C , Lee, S Y , Pitt, G S , Wang, C , Yan, H , Ef-hand , Iq-motif , Nav1 5 ctd binds to fgf13 and ... Crystal structure of the C-terminus of voltage-gated sodium channel in complex with FGF13 and CaM. ... May regulate voltage-gated sodium channels transport and function.[79] May also play a role in MAPK signaling.[80] ...
potassium voltage-gated channel modi.... KHDRBS3. 10656. KHDRBS3. "KH RNA binding domain containing, s.... ... NAV1. 89796. NAV1. neuron navigator 1 [Source:HGNC Symb.... NAV2. 89797. NAV2. neuron navigator 2 [Source:HGNC Symb.... ... transmembrane BAX inhibitor motif co.... TMEM165. 55858. TMEM165. transmembrane protein 165 [Source:HG.... ... sodium/potassium transporting ATPase.... NLGN1. 22871. NLGN1. neuroligin 1 [Source:HGNC Symbol;Acc.... ...
voltage-gated calcium channel complex. A protein complex that forms a transmembrane channel through which calcium ions may pass ... Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit. Nature, 1994 Mar ... properties of the alpha1 subunits as observed for the auxiliary subunits of voltage-dependent sodium and potassium channels ( ... voltage-gated calcium channel complex. A protein complex that forms a transmembrane channel through which calcium ions may pass ...
potassium voltage-gated channel, KQT-like subfamily, member 2. 0.011. CXCL14. chemokine (C-X-C motif) ligand 14. 0.011. ... solute carrier family 9 (sodium/hydrogen exchanger), member 3. 0.016. LAPTM4A. lysosomal protein transmembrane 4 alpha. 0.016. ... inhibitor of DNA binding 4, dominant negative helix-loop-helix protein. 0.017. ... NAV1. neuron navigator 1. 0.010. ECEL1. endothelin converting enzyme-like 1. 0.010. ...
Regulation of Cardiac Voltage-Gated Sodium Channel by Kinases: Roles of Protein Kinases A and C. Handb Exp Pharmacol. 2017;. * ... Biophysical characterization of the Varroa destructor NaV1 sodium channel and its affinity for τ-fluvalinate insecticide. FASEB ... Teneurin transmembrane protein 4 is not a cause for essential tremor in a Canadian population. Mov Disord. 2017;32(2):292-295. ... Withania somnifera Reverses Transactive Response DNA Binding Protein 43 Proteinopathy in a Mouse Model of Amyotrophic Lateral ...
  • A huge amount of disease-causing mutations have been recognized in transmembrane segments of Nav1.5. (
  • Interestingly, unlike additional C-terminal website truncating mutations [11], the mutation here presented did not modify INa,L suggesting that deletions of different lengths can differentially impact gating properties of the variants. (
  • Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. (
  • Human genetics studies of individuals with gain-of-function and loss-of-function mutations in the Nav1.7 channel have implicated Nav1.7 as playing a critical role in pain. (
  • Investigators from the University of British Columbia, Great Ormond Street Hospital for Children, and the National Hospital reported their findings on neurotransmitter deficiencies in two patients with mutations in voltage-gated sodium genes (SCN2A and SCN8A) discovered by whole exome sequencing. (
  • In this study examined a racially and ethnically diverse cohort of IBS patients for SCN5A missense mutations, and compared them to IBS negative controls, and determined the resulting NaV1. (
  • It concentrates multiple membrane proteins such as ion channels and cell adhesion molecules (CAMs) that are recruited to the AIS by the scaffold protein ankyrin G (ankG). (
  • Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. (
  • Loss of NF-186, NrCAM, Nav channels, or βIV spectrin did not affect other neuronal AIS proteins. (
  • Thus, the clustering of ion channels at nodes of Ranvier is thought to depend on binding to cytoskeletal and scaffolding proteins that are positioned along axons by extracellular, heterophilic interactions between axonal and glial CAMs ( Schafer and Rasband, 2006 ). (
  • Experiments utilizing squid axonal membranes indicate that sodium channel binding likely occurs on the internal face of the neuron. (
  • By analogy with nodes, the CAMs NF-186 and neuron glia-related CAM (NrCAM) may initiate ion channel clustering at the AIS through as-yet-unknown extrinsic mechanisms. (
  • This review article will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels at the neuronal plasma membrane and the regulatory mechanisms ensuring segregated functions. (
  • This review article summarizes current knowledge regarding potassium and sodium channels trafficking and surface expression and highlights the remaining questions regarding the mechanisms by which segregation of these ion channels at the plasma membrane is achieved. (
  • We focus on specific potassium and sodium VGCs: Kv1, Kv4.2 and Kv2.1 and Nav1.2, Nav1.6, respectively. (
  • Summary of localization, accessory subunits and physiological functions of voltage-gated potassium and sodium channels. (
  • The latter include calcium and sodium channels, chloride channels, potassium channels. (
  • Voltage dependent calcium channels (VDCC) auxiliary beta (Cavb1-4) and alpha2delta (Cava2d1-4) subunits associate with the alpha1 functional subunits (for review see Walker and De Waard, 1998 [1279] ) and affect the biophysical properties of the alpha1 subunits as observed for the auxiliary subunits of voltage-dependent sodium and potassium channels (for review see Isom et al. (
  • The toxicity of grayanotoxin is derived from its ability to interfere with voltage-gated sodium channels located in the cell membrane of neurons. (
  • Normally, voltage gated sodium channels are activated (opened) only when the cell membrane potential reaches a specific threshold voltage. (
  • Owing to its transient ability to activate channels and increase membrane permeability to sodium ions, grayanotoxin is classified as a reversible Nav1.x agonist. (
  • In rat cultured hippocampal neurons and cortical organotypic slices, we found that shRNA-mediated knockdown of ankG membrane partners (voltage-gated sodium channels (Nav) or neurofascin-186) led to a decrease of ankG concentration and perturbed the AIS formation and maintenance. (
  • These effects were rescued by expressing a recombinant AIS-targeted Nav or by a minimal construct containing the ankyrin-binding domain of Nav1.2 and a membrane anchor (mABD). (
  • channel gating and membrane expression. (
  • Heterologous manifestation of the mutation resulted in a marked decrease of maximum INa density primarily caused by a reduced channel trafficking toward the plasma membrane and in severe alterations in channel activation and inactivation. (
  • These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. (
  • A protein complex that forms a transmembrane channel through which calcium ions may pass in response to changes in membrane potential. (
  • Coexpression of beta subunits enhanced the level of channel expression in the plasma membrane (Williams et al. (
  • We will also discuss the relevance of proper ion channel targeting for neuronal physiology and how alterations in polarized distribution contribute to neuronal pathology. (
  • Genetic disorders that disrupt the function of these channels produce an array of Na(+) channelopathies resulting in neuronal impairment, chronic pain, neuromuscular pathologies, and cardiac arrhythmias. (
  • Human neuronal voltage-dependent calcium channels: studies on subunit structure and role in channel assembly. (
  • This activated conformation allows for an influx of sodium ions resulting in cell depolarization, followed by the firing of an action potential. (
  • The passage of ions into cells can be accomplished through specific ionotropic receptors or through specific ion channels that only conduct passage of ions. (
  • Intro gene encodes the -subunit of cardiac voltage-gated Na+ channels (Nav1.5), which generate the inward sodium current (INa) that is critical for the genesis and propagation of action potentials and, subsequently, determines cardiac conduction and excitability speed from the electrical impulse inside the center [1,2]. (
  • Nav1.5 comprises 4 homologous domains, DI to DIV, each which contains 6 transmembrane helices (S1 to S6) with intracellular N- and C-terminal domains [3]. (
  • The SCN5A-encoded voltage-gated mechanosensitive sodium (Na(+)) channel NaV1.5 is expressed in human GI smooth muscle cells and interstitial cells of Cajal. (
  • Touch and pressure on the skin lead to opening of mechanosensitive channels located within the sensory receptors. (
  • The Nav1.x channels consist of four homologous domains (I-IV), each containing six transmembrane alpha-helical segments (S1-S6). (
  • The resulting increase in [Ca2+ ]i activates a wide range of Ca2+ -dependent processes in neurons, including neurotransmitter release, gene transcription, activation of Ca2+ -dependent enzymes, and activation of certain K+ channels and chloride channels. (
  • Principles underlying their polarized distribution and function in neurons are better understood and might be paradigmatic to understand the mechanisms controlling the subcellular distribution and function of other ion channels present in axons and dendrites. (
  • X-ray and cryo-EM structures of tetrameric and pseudo-tetrameric P-loop channels are used to elaborate homology models of mammalian voltage-gated sodium channels with drugs and neurotoxins. (
  • Selectively slows channel inactivation of mammalian Nav1.1/SCN1A, Nav1.3/SCN3A, and Nav1.6/SCN8A and shows higher affinity for insect Nav1/para channels (site 3). (
  • Summary Despite a severe truncation of the C-terminus, the producing mutated channels generate currents, albeit with reduced amplitude and modified biophysical properties, confirming the key part of the C-terminal website in the manifestation and function of the cardiac Na+ channel. (
  • [92] found a novel inhibitory effect of b3 subunit on macroscopic Ba2+ currents through recombinant N- and R-type calcium channels expressed in Xenopus oocytes. (
  • Overexpressed Ca(v)beta3 inhibits N-type (Cav2.2) calcium channel currents through a hyperpolarizing shift of ultra-slow and closed-state inactivation. (
  • An important gene associated with Generalized Epilepsy with Febrile Seizures Plus is SCN1B (Sodium Voltage-Gated Channel Beta Subunit 1), and among its related pathways/superpathways are Developmental Biology and G-Beta Gamma Signaling . (
  • Paroxysmal Extreme Pain Disorder, also known as familial rectal pain , is related to mucocutaneous ulceration, chronic and brugada syndrome 1 , and has symptoms including pain An important gene associated with Paroxysmal Extreme Pain Disorder is SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and Developmental Biology . (
  • FLJ58949) encodes beta 3 subunit of voltage dependent calcium channels. (
  • High-voltage-activated calcium channels are comprised of a pore-forming alpha1 subunit, auxiliary beta and alpha2delta subunits, and, in some cases, an auxiliary gamma subunit (for review see Catterall, 2000 [477] ). (
  • Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function. (
  • Additional factors involved in specification of mechanoreceptors include the transcription factor MAF and the transmembrane receptor RET that interacts with the ligand GDNF (glial derived neurotrophic factor). (
  • When grayanotoxin is present, binding induces further conformational changes that prevent sodium channel inactivation and lead to a prolonged depolarization. (
  • It has been proposed that C-terminus helices participate in the control of inactivation through stabilization of the closed gate [9,10]. (
  • Action potential initiation and propagation requires clustered Na + (voltage-gated Na + [Nav]) channels at axon initial segments (AIS) and nodes of Ranvier. (
  • A critical determinant for the molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels (VGCs). (
  • Other toxins that bind to this region include the alkaloids veratridine, batrachotoxin and aconitine. (
  • Animal toxins are structurally diverse peptides that are highly potent yet selective on ion channel subtypes and therefore representing valuable probes to elucidate the structures, gating properties and cellular functions of ion channels. (
  • Grayanotoxin has a binding affinity (IC50) of approximately 10 μM and binds the group II receptor site located on segment 6 of domains I and IV (IS6 and IVS6). (
  • Sensory receptors General factors In considering sensory systems it is important to take into account initiating stimuli, cell membranes, cellular receptors, ion channels, ion pumps and intra-cellular signaling systems, particularly G- protein coupled systems. (
  • Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel. (
  • In contrast, the cellular and molecular mechanisms of nodal Nav channel clustering are better characterized. (
  • 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 conditions. (
  • Prolonged sodium channel activation and cell depolarization leads to overstimulation of the central nervous system. (
  • At the molecular level, the AIS is organized by ankyrin G (ankG), a specialized scaffolding protein that directly binds to the submembrane cytoskeletal lattice of ßIV-spectrin (ßIVsp) and actin. (
  • Introduction We functionally analyzed a frameshift mutation in the gene encoding cardiac Na+ channels (Nav1. (
  • The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. (
  • Hao et al.3 noted that influx of cations through these channels generated an electric potential that can be further amplified by voltage gated channels. (
  • At the peak of the action potential, voltage-gated sodium channels are quickly inactivated and are only reset once the cell has repolarized to resting potential. (
  • Several studies show an uneven distribution of ion channels and their differential regulation within dendrites and axons, which is a prerequisite for an appropriate integration of synaptic inputs and the generation of adequate action potential (AP) firing patterns. (
  • whereas rapid and efficient action potential conduction along axons depends on high densities of Nav channels located at nodes of Ranvier. (
  • Voltage-gated sodium channels (Navs) play critical roles in action potential generation and propagation. (
  • It has been shown that b auxiliary subunits increase current amplitude in voltage-dependent calcium channels (Mori et al. (
  • Selective Ligands and Drug Discovery Targeting the Voltage-Gated Sodium Channel Nav1.7. (
  • Although the identification and development of selective Nav channel modulators have historically been challenging, a number of recent publications has demonstrated progression of increasingly subtype-selective small molecules and peptides toward potential use in preclinical or clinical studies. (
  • Voltage-gated sodium (Na(+)) channels are expressed in virtually all electrically excitable tissues and are essential for muscle contraction and the conduction of impulses within the peripheral and central nervous systems. (
  • Because of their importance to the conduction of electrical signals, Na(+) channels are the target of a wide variety of local anesthetic, antiarrhythmic, anticonvulsant, and antidepressant drugs. (
  • µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. (
  • We identified high-confidence PAX3-FOXO1 target genes by a series of criteria: first, using only PAX3-FOXO1 bound to enhancers recurrent in cell lines and tumors. (
  • Furthermore, C-terminal website bears several regions critical for protein-protein connection, particularly the PDZ binding website, which, in turn, are critical for channel trafficking and surface manifestation. (
  • The base structure is a 5/7/6/5 ring system that does not contain nitrogen. (
  • This chapter outlines sodium channel models with local anesthetics, anticonvulsants, and antiarrhythmics, which are used to manage pain and treat sodium channelopathies. (
  • Schwann cells initiate peripheral nervous system node formation by clustering NF-186, which then recruits ankyrinG and Nav channels. (
  • Mechanisms of Drug Binding to Voltage-Gated Sodium Channels. (
  • The voltage-gated sodium (Nav) channel Nav1.7 has been the focus of intense investigation in recent years. (
  • Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors from venomous animals. (