Sodium Channels: 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.Sodium Channel Blockers: 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.Ion Channels: 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.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.NAV1.8 Voltage-Gated Sodium Channel: 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.Epithelial Sodium Channels: 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.NAV1.2 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.NAV1.5 Voltage-Gated Sodium Channel: 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.NAV1.7 Voltage-Gated Sodium Channel: 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.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.NAV1.6 Voltage-Gated Sodium Channel: 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.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Voltage-Gated Sodium Channels: 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.NAV1.1 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3.NAV1.3 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype found in neuronal tissue that mediates the sodium ion PERMEABILITY of excitable membranes.NAV1.4 Voltage-Gated Sodium Channel: 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.NAV1.9 Voltage-Gated Sodium Channel: 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.Sodium Channel Agonists: A class of drugs that stimulate sodium influx through cell membrane channels.Membrane Potentials: 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).Electrophysiology: 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.Tetrodotoxin: 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.Saxitoxin: A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Patch-Clamp Techniques: 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.Batrachotoxins: 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.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Potassium Channel Blockers: 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.Voltage-Gated Sodium Channel Blockers: A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.Oocytes: 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).Potassium Channels, Voltage-Gated: 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.Scorpion Venoms: 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.Xenopus laevis: 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.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Veratridine: A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.Voltage-Gated Sodium Channel beta-1 Subunit: A voltage-gated sodium channel beta subunit abundantly expressed in SKELETAL MUSCLE; HEART; and BRAIN. It non-covalently associates with voltage-gated alpha subunits. Defects in the SCN1B gene, which codes for this beta subunit, are associated with generalized epilepsy with febrile seizures plus, type 1, and Brugada syndrome 5.Potassium: 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.Kinetics: The rate dynamics in chemical or physical systems.Shaker Superfamily of Potassium Channels: 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.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Epithelial Sodium Channel Blockers: A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.KATP 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.Lidocaine: 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, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Amiloride: 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)Voltage-Gated Sodium Channel beta-3 Subunit: 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.Ranvier's Nodes: 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.Neurons: 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.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: 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.Large-Conductance Calcium-Activated Potassium Channels: 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.Acid Sensing Ion Channels: 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.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.Cyclic Nucleotide-Gated Cation Channels: 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.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.Ganglia, Spinal: 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.Voltage-Gated Sodium Channel beta-2 Subunit: A voltage-gated sodium channel beta subunit that binds covalently to voltage-gated alpha subunits.Calcium Channels, T-Type: 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.Pyrethrins: 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.Mexiletine: Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.Voltage-Gated Sodium Channel beta-4 Subunit: 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.Degenerin Sodium Channels: A family of mechanosensitive sodium channels found primarily in NEMATODES where they play a role in CELLULAR MECHANOTRANSDUCTION. Degenerin sodium channels are structurally-related to EPITHELIAL SODIUM CHANNELS and are named after the fact that loss of their activity results in cellular degeneration.Calcium: 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.Rats, Sprague-Dawley: 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.Conotoxins: 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)Nerve Tissue ProteinsMutation: 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.Decapodiformes: 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.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.TRPC Cation Channels: 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.Ether-A-Go-Go Potassium Channels: A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Erythromelalgia: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cockroaches: Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.Scorpions: 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)Protein Subunits: 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.Ion Transport: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Neurotoxins: 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.Cells, Cultured: 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.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.Epithelial Sodium Channel Agonists: Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION CHANNELS.Sodium, Dietary: Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.Models, Biological: 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.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Calcium Channel Agonists: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.Myotonia: 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.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Time Factors: Elements of limited time intervals, contributing to particular results or situations.TRPV Cation Channels: 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.Barium: 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.Sodium Chloride: A ubiquitous sodium salt that is commonly used to season food.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.Anesthetics, Local: 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.TRPM Cation Channels: 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.Myocardium: 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.Oxocins: Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)Marine Toxins: 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.Spider Venoms: 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.Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.KCNQ Potassium Channels: 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.Cnidarian Venoms: 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.Kv1.5 Potassium Channel: 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.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: 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.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.Heart: The hollow, muscular organ that maintains the circulation of the blood.Shab Potassium Channels: 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.Biophysical Phenomena: The physical characteristics and processes of biological systems.Small-Conductance Calcium-Activated Potassium Channels: 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.Amphibian Proteins: Proteins obtained from species in the class of AMPHIBIANS.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Electrophorus: 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.Hydrogen-Ion Concentration: 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)Guinea Pigs: 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.KCNQ2 Potassium Channel: A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.Transfection: 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.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.SemicarbazonesBinding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Channelopathies: A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.Shal Potassium Channels: 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.RNA, Complementary: 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)Potassium Channels: 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.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Transient Receptor Potential Channels: A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Cesium: 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.Anti-Arrhythmia Agents: 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.Synaptosomes: 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.Structure-Activity Relationship: 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.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Rabbits: 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.Ciguatoxins: 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.Long QT Syndrome: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.Brugada 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.Adenosine Triphosphate: 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.Insecticides: 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.Muscles: Contractile tissue that produces movement in animals.Large-Conductance Calcium-Activated Potassium Channel alpha Subunits: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Tetraethylammonium CompoundsAnkyrins: 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.G Protein-Coupled Inwardly-Rectifying Potassium Channels: 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.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Paralyses, Familial Periodic: A heterogenous group of inherited disorders characterized by recurring attacks of rapidly progressive flaccid paralysis or myotonia. These conditions have in common a mutation of the gene encoding the alpha subunit of the sodium channel in skeletal muscle. They are frequently associated with fluctuations in serum potassium levels. Periodic paralysis may also occur as a non-familial process secondary to THYROTOXICOSIS and other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1481)Electrophysiological Phenomena: 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.Protein Conformation: 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).Brain: 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.Muscle, Skeletal: 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.Ryanodine Receptor Calcium Release Channel: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.RNA, Messenger: 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.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Acetanilides: 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.Mollusk Venoms: 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.Kidney Tubules, Collecting: 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.Mutation, Missense: 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)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Sea Anemones: The order Actiniaria, in the class ANTHOZOA, comprised of large, solitary polyps. All species are carnivorous.KCNQ3 Potassium Channel: 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.Aldosterone: 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.Epilepsies, Myoclonic: 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.).Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.Benzocaine: A surface anesthetic that acts by preventing transmission of impulses along NERVE FIBERS and at NERVE ENDINGS.Voltage-Dependent Anion Channels: 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.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Intermediate-Conductance Calcium-Activated Potassium Channels: 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.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Rana pipiens: A highly variable species of the family Ranidae in Canada, the United States and Central America. It is the most widely used Anuran in biomedical research.VeratrineHeart Conduction System: An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.CHO Cells: 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.Hypokalemic Periodic Paralysis: An autosomal dominant familial disorder characterized by recurrent episodes of skeletal muscle weakness associated with falls in serum potassium levels. The condition usually presents in the first or second decade of life with attacks of trunk and leg paresis during sleep or shortly after awakening. Symptoms may persist for hours to days and generally are precipitated by exercise or a meal high in carbohydrates. (Adams et al., Principles of Neurology, 6th ed, p1483)Spiders: 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)Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Protein Binding: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Sensory Receptor Cells: Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.Rana esculenta: An edible species of the family Ranidae, occurring in Europe and used extensively in biomedical research. Commonly referred to as "edible frog".Membrane Proteins: 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.Contactins: A family of immunoglobulin-related cell adhesion molecules that are involved in NERVOUS SYSTEM patterning.Dogs: 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)Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.Periplaneta: A genus in the family Blattidae containing several species, the most common being P. americana, the American cockroach.Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Paralysis, Hyperkalemic Periodic: An autosomal dominant familial disorder which presents in infancy or childhood and is characterized by episodes of weakness associated with hyperkalemia. During attacks, muscles of the lower extremities are initially affected, followed by the lower trunk and arms. Episodes last from 15-60 minutes and typically occur after a period of rest following exercise. A defect in skeletal muscle sodium channels has been identified as the cause of this condition. Normokalemic periodic paralysis is a closely related disorder marked by a lack of alterations in potassium levels during attacks of weakness. (Adams et al., Principles of Neurology, 6th ed, p1481)Mathematics: The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
"Voltage gated", also called "voltage sensitive" and "voltage dependant" sodium channel also known as "VGSCs" or "Nav channel" ... Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Sodium-channel ... that may be modulated by concurrent microorganism; and, last but not least, because of the specific properties of each kind of ... of some voltage gated sodium channels in a very powerful and reversible manner, without affection of other ion channels. " ...
"Sodium Channel NaV1.5 Expression is Enhanced in Cultured Adult Rat Skeletal Muscle Fibers, The Journal of Membrane Biology" on ... Beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct ... lp/springer_journal/sodium-channel-nav1-5-expression-is-enhanced-in-cultured-adult-rat-lAZWCBiJ8J ... Differences in sodium voltage-gated channel properties according to myosin heavy chain isoform expression in single muscle ...
"Voltage gated", also called "voltage sensitive" and "voltage dependant" sodium channel also known as "VGSCs" or "Nav channel" ... Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Sodium-channel ... that may be modulated by concurrent microorganism; and, last but not least, because of the specific properties of each kind of ... of some voltage gated sodium channels in a very powerful and reversible manner, without affection of other ion channels. " ...
Another family of membrane proteins that modulate synaptic activity are the voltage gated sodium channels (NAvs). Recently, the ... CK2 was further found to directly phosphorylate the voltage gated sodium channel NAv1, thereby enhancing its binding to ankyrin ... CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability. FASEB J. ... of the fibroblast growth factor receptor FGF14 and reduced interaction of FGF14 with voltage gated sodium channels (NAv1.2 and ...
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 . Gene expansion has shaped ...
However, studies should further explore the effects of inflammatory cytokines on voltage-gated sodium channels (VGSCs) and ... ligand-5, IL-10, and transforming growth factor-β1, at 6 and 24 h after injury. Incubation in trauma-conditioned medium ... Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and ... CXCL13/CXCR5 enhances sodium channel Nav1. 8 current density via p38 MAP kinase in primary sensory neurons following ...
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 ... ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. ...
Voltage-gated sodium channels belong to the superfamily of voltage-gated cation channels. Their structure is based on domains ... However, ion channels are heterogeneous multi-molecular complexes that are extensively modulated and undergo a maturation ... www.readbyqxmd.com/read/28597987/trafficking-and-localization-to-the-plasma-membrane-of-nav-1-5-promoted-by-the-%C3%AE-2- ... the α subunit of the major cardiac voltage-gated sodium channel. This channel forms a protein complex including one or two ...
The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci. 2006;26( ... Flexible Accelerated STOP Tetracycline operator-knockin (FAST): a versatile and efficient new gene modulating system. Biol ... Functional analysis of stably expressed human Nav1. Biophys J. 2012;102:527a. ... Ahern CA, Payandeh J, Bosmans F, Chanda B. The hitchhikers guide to the voltage-gated sodium channel galaxy. J Gen Physiol. ...
The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope-tagged NaV1.7 mouse ... www.readbyqxmd.com/read/29335280/mapping-protein-interactions-of-sodium-channel-nav1-7-using-epitope-tagged-gene-targeted-mice ... Eukaryotic cyclic nucleotide-modulated channels perform their diverse physiological roles by opening and closing their pores to ... Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the ...
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 ... cells and in addition modulates T-cell activation and differentiation (5C9). IL-1 was proven to straight inhibit islet insulin ... Loss-of-function mutations in the gene encoding voltage-gated sodium route Nav1. Nav1.7-null mutant mice, aswell as with a ...
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 ... to CD2 and plays a role as an accessory molecule in g/d T cell recognition and a/b T cell antigen recognition channel gating ... Copyright © 2020 p53 modulates acquired resistance to EGFR inhibitors , Powered by zBench and WordPress ...
... also known as sodium channel protein type 9 subunit alpha, neuroendocrine sodium channel, hNE-Na and peripheral sodium channel ... Laedermann CJ, Syam N, Pertin M, Decosterd I, Abriel H.. (2013), β1- and β3- voltage-gated sodium channel subunits modulate ... Peripheral sodium channel 1) (PN1) (Sodium channel protein type IX subunit alpha) (Voltage-gated sodium channel subunit alpha ... also known as sodium channel protein type 9 subunit alpha, neuroendocrine sodium channel, hNE-Na and peripheral sodium channel ...
... 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 ...
Behavioural Brain Research herpes, v. Abnormal expression of voltage-gated sodium channels Nav1. Neurosciencev. Remote ... Deep brain stimulation of the dentate nucleus improves ataxia and modulates cortical excitability. S, Intraoperative assistive ... Serum sodium disorders in patients with traumatic brain injury.. Therapeutics and Clinical Risk Management Zoster em ... Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson? Insular gliomas and ...
... including the voltage-gated sodium channel (Nav1) β2 subunit, Golgi-localized membrane-bound α2,6-sialyltransferase, P-selectin ... Clathrin-modulated endocytosis is tightly controlled, requiring the participation of AP-2, dynamin I, and many other factors [ ... and had subtle electrophysiological alterations in the steady-state inactivation of their voltage-gated sodium channels. They ... Hu X, Hicks CW, He W, Wong P, Macklin WB, Trapp BD, Yan R: Bace1 modulates myelination in the central and peripheral nervous ...
Heterogeneous expression of voltage-gated potassium channels in the heart: roles in normal excitation and arrhythmias ... Molecular identity of the late sodium current in adult dog cardiomyocytes identified by Nav1. 5 antisense inhibition ... Transmural variation in myosin heavy chain isoform expression modulates the timing of myocardial force generation in porcine ... Na+ channel distribution and electrophysiological heterogeneities in guinea pig ventricular wall. Osadchii, OE; Soltysinska, E ...
... pathway in the development of postoperative chronic pain and the relationship with ex-pression of voltage-gated sodium channel ... 01). Conclusion Up-regulated expression of Nav1. 7 in DRGs after activating TLR4/NF-κB signaling pathway is involved in the ... modulating multiple functions, such as cell proliferation, migration, differentiation, apoptosis, senescence, and inflammatory ... Chloride Channel-3 (ClC-3) is a member of the Cl2 channel superfamily,which is encoded by CLCN3 gene.It involves regulating ...
Both substances were previously demonstrated to quite potently inhibit neuronal voltage-gated Na(+) channels. Thus, a possible ... The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation ... Propofol (IC50 126 ± 47 μM) and dexmedetomidine (IC50 182 ± 27 μM) blocked the persistent sodium current induced by veratradine ... molecular mechanism for some of their cardiac side effects is an inhibition of cardiac voltage gated Na(+) channels. In this ...
Crystal structure of the C-terminus of voltage-gated sodium channel in complex with FGF13 and CaM. ... on mechanisms of permeation and voltage-dependent gating but less is known about how intracellular domains modulate channel ... 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 ... Voltage-gated Na(+) (Na(V)) channels initiate neuronal action potentials. Na(V) channels are composed of a transmembrane domain ...
... the KCNQ2 potassium channel (Pan et al., 2006) and also the voltage-gated calcium channel Cav1.three (Cunha et al., 2011), for ... in addition to release of intracellular calcium stores and influxes through L-type cation channel and sodium-calcium exchanger ... TRPM5 modulates ATP-induced Ca2+ entry. (A) Time course of imply Ca2+ responses (Fura-2 ratio) Lanoconazole web obtained in ... repeats prevents Nav1.two and Nfasc ABDs from binding to AnkG_repeats. DOI: 10.7554/eLife.04353.011 Figure supplement two. ITC- ...
voltage-gated sodium channel complex. A sodium channel in a cell membrane whose opening is governed by the membrane potential. ... Beta1-subunit modulates the Nav1.4 sodium channel by changing the surface charge. , 2006 Jun , 172 (139-50).. ... Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer. Oncol. Rep., 2010 May , 23 (1293-9).. ... sodium channel, voltage-gated, type IV, alpha subunit. Synonyms: nav1.4 scn4a. Symbol: Scn4a ...
Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje ... AnkG is required for AIS formation. (A) 10-DIV hippocampal neurons transfected with Nav channel shRNA (Nav1.x shRNA), ankG ... The nervous system is a highly integrated network of neurons and glia that work together to generate, propagate, and modulate ... voltage-gated Na+ [Nav]) channels at axon initial segments (AIS) and nodes of Ranvier. In addition to ion channels, these ...
... encodes the voltage-gated sodium channel alpha subunit, type X, Na1.8. SCN10A encodes a TTX-resistant channel that is ... and these subunits interact and modulate the channel.. *. b1-subunit alone, or in combination with other b-subunits, ... A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature, 1996 Jan 18 , 379 (257-62). ... A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A. Pain, 1998 Nov , 78 (107-14 ...
... inactivating Nav1.4 voltage-gated sodium channels at the NMJ, and consequently blocking the production of muscle action ... Because astrocytes express an abundance of transporters and ion channels that modulate the levels of these ions in response to ... Accumulation of Nav1 mRNAs at differentiating postsynaptic sites in rat soleus muscles * MA Stocksley ... followed by activation of voltage-gated sodium channels (VGSC), leading to action potentials and contraction of muscle (brown ...
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 ... Sphingosine 1-Phosphate Receptor 1 Modulates CNTF-Induced Axonal Growth and Neuroprotection in the Mouse Visual System. Neural ... A leaky voltage sensor domain of cardiac sodium channels causes arrhythmias associated with dilated cardiomyopathy. Sci Rep. ...
SubunitsInactivationCurrentsMammalianNeuronsMutationsNav1.52018Nav1.7Skeletal muscleMembraneInhibitorsCorticalPotassium2017DepolarizationChannelopathiesTetrodotoxinCardiacBindsEncodesPeripheralVertebrateNerveSubtypesConductanceSensoryCellsMembranesAmplitudeReceptorExpressionMolecularRolesDependenceSegmentsCalciumLocal anestheticRegulation
- Our data evidenced an increase in NaV1.5 channels and the involvement of β subunits in the regulation of sodium current and fiber excitability. (deepdyve.com)
- Sodium-channel proteins in the mammalian brain are composed of an association that include one alpha subunit and one or more auxiliary beta subunits. (wikipedia.org)
- Nine types of alpha subunits have been described (Nav1.1 to Nav1.9), and a tenth related isoform (Nax) may also play some role as a Nav channel. (wikipedia.org)
- Laedermann CJ, Syam N, Pertin M, Decosterd I, Abriel H.. (2013), ' β1- and β3- voltage-gated sodium channel subunits modulate cell surface expression and glycosylation of Nav1.7 in HEK293 cells. . (antibodiesinc.com)
- Summary of localization, accessory subunits and physiological functions of voltage-gated potassium and sodium channels. (frontiersin.org)
- Nav1.8 is likely to be co-expressed with the b1, b2, and b3-subunits in C-fiber neurons from the DRG, and these subunits interact and modulate the channel. (epfl.ch)
- b1-subunit alone, or in combination with other b-subunits, accelerates the time constant of inactivation and shifts the voltage-dependence of activation to more hyperpolarized potentials. (epfl.ch)
- Co-expression of b1 and b3-subunits with Nav1.8 resulted in little change in availability compared to channel alone. (epfl.ch)
- Site 3 binds alpha-scorpion and sea anemone toxins, which slow sodium channel inactivation. (wikipedia.org)
- It has been proposed that C-terminus helices participate in the control of inactivation through stabilization of the closed gate [9, (boothampitheatre.com)
- 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. (boothampitheatre.com)
- The voltage dependencies of fast and slow inactivation as well as the time course of recovery from inactivation were shifted by both propofol and dexmedetomidine. (jpt.com)
- Calmodulin also was able to modulate the inactivation kinetics of Nav1.6, but not Nav1.4, currents in a calcium-dependent manner. (epfl.ch)
- one of them, the III-IV linker, contains the supposed inactivation particle of the channel. (epfl.ch)
- Nav1.8 is found only within small-diameter sensory neurons in the periphery generating electrical impulses and transmiting nociceptive information to the central nervous system in cold temperatures, unlike the other sodium channels which have enhanced slow inactivation with cooling . (epfl.ch)
- Steady-state inactivation of Nav1.8 and Nav1.7 channels was also affected by lidocaine, Nav1.7 being the most sensitive. (epfl.ch)
- Only the steady-state activation of Nav1.8 was affected while the entry of both channels into slow inactivation was affected by lidocaine, Nav1.8 being affected to a larger degree. (epfl.ch)
- b3-subunit shifts the voltage-dependence of inactivation to more positive potentials and do not influence the time constant of current decay, steadystate activation or expression of Nav1.8. (epfl.ch)
- use-dependent reduction of Nav1.8 current in IB4+ neurons is significantly stronger than that in IB4- neurons, although voltage dependency of activation and steady-state inactivation are not different. (epfl.ch)
- 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. (boothampitheatre.com)
- 2012). Nonetheless, we detected neither voltage-gated whole-cell Ca2+ currents (Figure 9-figure supplement 1A) nor depolarization-induced Ca2+ signals (Figure 9-figure supplement 1B) in starved N2 cells. (pteninhibitor.com)
- Nav1.8 channels interact with various commercially available compounds such as menthol, lidocaine, tetracaine, vinpocetine, ambroxol, lamotrigine, mexilitine, veratridine, and A-803467, whereas very few animal toxins have been shown to be capable of reshaping Nav1.8 currents . (epfl.ch)
- For example, lidocaine , suppresses Na+ currents by binding not only to DIV-S6 but also to S6 of DI and DII, blocking the channels in a use-dependent (frequency-dependent) and voltage-dependent manner , . (epfl.ch)
- Voltage gated", also called "voltage sensitive" and "voltage dependant" sodium channel also known as "VGSCs" or "Nav channel" are crucial elements of normal physiology in a variety of animals, including flies, leeches, squid and jellyfish, as well as mammalian and non-mammalian vertebrates. (wikipedia.org)
- 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. (readbyqxmd.com)
- However, studies should further explore the effects of inflammatory cytokines on voltage-gated sodium channels (VGSCs) and excitability in distal intact neurons. (biomedcentral.com)
- 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. (frontiersin.org)
- The nervous system is a highly integrated network of neurons and glia that work together to generate, propagate, and modulate action potentials. (rupress.org)
- The channel is expressed only by small-diameter sensory neurons in neonatal and adult dorsal root and trigeminal ganglia . (epfl.ch)
- Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. (mdpi.com)
- 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. (readbyqxmd.com)
- 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. (readbyqxmd.com)
- Furthermore, loss-of-function Nav1.5 mutations have already been described in sufferers with idiopathic ventricular fibrillation (IVF), an uncommon and lethal condition which occurs as syncope or sudden cardiac loss of life in teenagers with normal hearts and without electrophysiological manifestations of inherited arrhythmogenic syndromes [5- (boothampitheatre.com)
- Interestingly, unlike additional C-terminal website truncating mutations , the mutation here presented did not modify INa,L suggesting that deletions of different lengths can differentially impact gating properties of the variants. (boothampitheatre.com)
- After 4 days of culture, an increase of the NaV1.5 channel type was observed. (deepdyve.com)
- These channels exhibited increased activation time constant (τm) and reduced conductance, similar to what has been observed in denervated muscles in vivo, where the density of NaV1.5 was increasing progressively after denervation. (deepdyve.com)
- The SCN5A-encoded voltage-gated mechanosensitive sodium (Na(+)) channel NaV1.5 is expressed in human GI smooth muscle cells and interstitial cells of Cajal. (readbyqxmd.com)
- 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, (boothampitheatre.com)
- In this study, we therefore explored the effects of propofol and dexmedetomidine on the cardiac predominant Na(+) channel α-subunit Nav1.5. (jpt.com)
- Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene-targeted mice. (readbyqxmd.com)
- The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. (readbyqxmd.com)
- We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. (readbyqxmd.com)
- Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo The sodium channel β3 (Scn3b), rather than the β1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing-response mediator protein (Crmp2) and Nav1. (readbyqxmd.com)
- 2013), ' Functional expression of the voltage-gated Na⁺-channel Nav1.7 is necessary for EGF-mediated invasion in human non-small cell lung cancer cells. . (antibodiesinc.com)
- Gueret, G. 2010-06-02 00:00:00 This study analyzes changes in the distribution, electrophysiological properties, and proteic composition of voltage-gated sodium channels (NaV) in cultured adult rat skeletal muscle fibers. (deepdyve.com)
- The action of NSTX produces minimal effect on cardiac Nav, where it exhibits about 20-60 fold lesser affinity than in Nav channels from rat skeletal muscle and rat brain. (wikipedia.org)
- The skeletal muscle a subunit functions as ion-conducting channel and consists of large polypeptides (1700-2000 amino acids) that fold into four highly homologous somains (repeats I-IV) containing six transmembrane segments each (S1-S6). (epfl.ch)
- Amino acid Ile-1575 in the middle of transmembrane segment 6 of domain IV (DIV-S6) in the adult rat skeletal muscle isoform of the voltage-gated sodium channel (rNaV1.4) may act as molecular switch allowing for interaction between outer and inner vestibules. (epfl.ch)
- Such functions include protease inhibitors, membrane pore formation, ion channel blockers and metal binding proteins. (mdpi.com)
- channel gating and membrane expression. (boothampitheatre.com)
- 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. (frontiersin.org)
- TRPM5 could be involved in modulating Ca2+ influx by changing the cell membrane possible following the entry of monovalent cations. (pteninhibitor.com)
- Optimistic modulation of Ca2+ entry by TRPM5-mediated membrane depolarization has been linked towards the activation of voltage-gated Ca2+ channels (Colsoul et al. (pteninhibitor.com)
- A sodium channel in a cell membrane whose opening is governed by the membrane potential. (epfl.ch)
- Beta-1 also increases levels of Nav1.8 channel functional expression, either by increasing channel density at the oocyte membrane or by increasing individual channel conductance. (epfl.ch)
- Toxin-like functions were revealed using ClanTox, a statistical machine-learning predictor trained on ion channel inhibitors from venomous animals. (mdpi.com)
- Accordingly, inhibitors of voltage-gated Ca2+ channels didn't modify ATP-mediated Ca2+ signals (Figure 9-figure supplement 1C). (pteninhibitor.com)
- Mechanical injury in mixed cortical neuron-astrocyte cultures significantly increased expression levels of multiple cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, chemokine (C-C motif) ligand-5, IL-10, and transforming growth factor-β1, at 6 and 24 h after injury. (biomedcentral.com)
- Former five, but more recently, six neurotoxin receptor sites have been recognized between the seven receptor site located in the vertebrate sodium channel receptor alpha subunit: Site 1 binds the sodium channel blockers tetrodotoxin and saxitoxin. (wikipedia.org)
- Toxins such as neosaxitoxin and tetrodotoxin have less affinity for most cardiac Nav channels than for most Nav channels in nerve tissue. (wikipedia.org)
- Voltage-gated, tetrodotoxin-resistant (TTX-R) Nav1.8 channels are expressed in both IB4+ and IB4- cells and produce most of the current underlying the depolarizing phase of action potential (AP). (epfl.ch)
- Introduction We functionally analyzed a frameshift mutation in the gene encoding cardiac Na+ channels (Nav1. (boothampitheatre.com)
- Inhibition of the Cardiac Na+ Channel α-subunit Nav1. (jpt.com)
- Thus, a possible molecular mechanism for some of their cardiac side effects is an inhibition of cardiac voltage gated Na(+) channels. (jpt.com)
- Site 2 binds lipid-soluble sodium channel activators such as veratridine. (wikipedia.org)
- Site 5 binds the polyether ladder brevetoxins and ciguatoxin. (wikipedia.org)
- Local anesthetic receptor site binds local anesthetics, antiarrhythmic drugs and antiepileptic drugs NSTX and other site 1 blockers have high affinity (very low dissociation constant) and high specificity for Nav channels. (wikipedia.org)
- CAP-1A binds to a conserved motif present in NaV1.8 linking voltage-gated sodium channels to clathrin, which is involved in coated vesicle assembly. (epfl.ch)
- 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. (readbyqxmd.com)
- Schwann cells initiate peripheral nervous system node formation by clustering NF-186, which then recruits ankyrinG and Nav channels. (rupress.org)
- 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. (mdpi.com)
- 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. (readbyqxmd.com)
- Here, we report a new clinical case of debilitating itch and altered pain perception resulting from the heterozygous de novo p.L811P gain-of-function mutation in Na V 1.9, a voltage-gated sodium (Na V ) channel subtype that relays sensory information from the periphery to the spine. (jci.org)
- Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson? (migroup.pro)
- The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes are essential to produce the differences in Ca2+ transients and contraction profiles via cooperative mechanisms of mechano-calcium-electric feedback and may further slightly modulate transmural differences in the electrical properties between the cells. (deepdyve.com)
- Our model is a useful tool to study the effects of denervation in adult muscle fibers in vitro and the expression of sodium channels. (deepdyve.com)
- A critical determinant for the molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels (VGCs). (frontiersin.org)
- 5. Biological function enrichment and KEGG pathway analysis of APOH gene， which was among the top ten key genes screened，was analyzed by Cytoscape and R，for further validation of expression of APOH in chronic hepatitis B virus-related liver failure. (bvsalud.org)