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.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.Mexiletine: Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.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.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.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.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.SemicarbazonesVoltage-Gated Sodium Channel Blockers: A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.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.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)Disopyramide: A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.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.NAV1.2 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.NAV1.6 Voltage-Gated Sodium Channel: 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.Ajmaline: An alkaloid found in the root of RAUWOLFIA SERPENTINA, among other plant sources. It is a class Ia antiarrhythmic agent that apparently acts by changing the shape and threshold of cardiac action potentials.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.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.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).Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.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.Epithelial Sodium Channel Blockers: A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.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.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.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Sodium Channel Agonists: A class of drugs that stimulate sodium influx through cell membrane channels.Mononeuropathies: Disease or trauma involving a single peripheral nerve in isolation, or out of proportion to evidence of diffuse peripheral nerve dysfunction. Mononeuropathy multiplex refers to a condition characterized by multiple isolated nerve injuries. Mononeuropathies may result from a wide variety of causes, including ISCHEMIA; traumatic injury; compression; CONNECTIVE TISSUE DISEASES; CUMULATIVE TRAUMA DISORDERS; and other conditions.Benzomorphans: Morphine derivatives of the methanobenzazocine family that act as potent analgesics.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.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)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.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.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.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.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.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.Bundle-Branch Block: A form of heart block in which the electrical stimulation of HEART VENTRICLES is interrupted at either one of the branches of BUNDLE OF HIS thus preventing the simultaneous depolarization of the two ventricles.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.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.ThiazinesScorpion 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.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.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.Electrocardiography: Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY.Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.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.Veratridine: A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.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.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).Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.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.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.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Heart 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.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.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.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.Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.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)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.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.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Kinetics: The rate dynamics in chemical or physical systems.Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.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.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.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.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.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)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.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.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.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.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.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.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.Kv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.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.4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.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.Nitrobenzoates: Benzoic acid or benzoic acid esters substituted with one or more nitro groups.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.Kv1.2 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.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.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)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.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.Cockroaches: Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.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.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.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.Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Kv1.1 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.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.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.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.Voltage-Gated Sodium Channel beta-2 Subunit: A voltage-gated sodium channel beta subunit that binds covalently to voltage-gated alpha subunits.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.Mutation: 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.Sodium, Dietary: Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.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.Nicardipine: A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.Epithelial Sodium Channel Agonists: Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION CHANNELS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Sodium Chloride: A ubiquitous sodium salt that is commonly used to season food.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.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.Oxocins: Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.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.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.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.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Amlodipine: A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.omega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.Angiotensin II Type 1 Receptor Blockers: Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Nerve Tissue ProteinsGuinea 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.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.Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.Nitrendipine: A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.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.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.omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.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.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.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.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.Niflumic Acid: An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.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.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.Tetraethylammonium CompoundsModels, 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.Diuretics: Agents that promote the excretion of urine through their effects on kidney function.Heart: The hollow, muscular organ that maintains the circulation of the blood.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Amphibian Proteins: Proteins obtained from species in the class of AMPHIBIANS.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.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Shaw Potassium Channels: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.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.Kv1.4 Potassium Channel: A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.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)4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid: An inhibitor of anion conductance including band 3-mediated anion transport.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.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.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.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.Antihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.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.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.omega-Agatoxin IVA: A neuropeptide toxin from the venom of the funnel web spider, Agelenopsis aperta. It inhibits CALCIUM CHANNELS, P-TYPE by altering the voltage-dependent gating so that very large depolarizations are needed for channel opening. It also inhibits CALCIUM CHANNELS, Q-TYPE.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.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.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.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.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.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.Delayed Rectifier Potassium Channels: A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.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.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.Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.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.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Decanoic Acids: 10-carbon saturated monocarboxylic acids.Isradipine: A potent antagonist of CALCIUM CHANNELS that is highly selective for VASCULAR SMOOTH MUSCLE. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure.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.Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.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.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Ions: 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.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)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.Riluzole: A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.

Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule. (1/1462)

While studying the adult rat skeletal muscle Na+ channel outer vestibule, we found that certain mutations of the lysine residue in the domain III P region at amino acid position 1237 of the alpha subunit, which is essential for the Na+ selectivity of the channel, produced substantial changes in the inactivation process. When skeletal muscle alpha subunits (micro1) with K1237 mutated to either serine (K1237S) or glutamic acid (K1237E) were expressed in Xenopus oocytes and depolarized for several minutes, the channels entered a state of inactivation from which recovery was very slow, i.e., the time constants of entry into and exit from this state were in the order of approximately 100 s. We refer to this process as "ultra-slow inactivation". By contrast, wild-type channels and channels with the charge-preserving mutation K1237R largely recovered within approximately 60 s, with only 20-30% of the current showing ultra-slow recovery. Coexpression of the rat brain beta1 subunit along with the K1237E alpha subunit tended to accelerate the faster components of recovery from inactivation, as has been reported previously of native channels, but had no effect on the mutation-induced ultra-slow inactivation. This implied that ultra-slow inactivation was a distinct process different from normal inactivation. Binding to the pore of a partially blocking peptide reduced the number of channels entering the ultra-slow inactivation state, possibly by interference with a structural rearrangement of the outer vestibule. Thus, ultra-slow inactivation, favored by charge-altering mutations at site 1237 in micro1 Na+ channels, may be analogous to C-type inactivation in Shaker K+ channels.  (+info)

Tetraethylammonium block of the BNC1 channel. (2/1462)

The brain Na+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family. Mutation of a specific residue (Gly430) that lies N-terminal to the second membrane-spanning domain activates BNC1 and converts it from a Na+-selective channel to one permeable to both Na+ and K+. Because all K+ channels are blocked by tetraethylammonium (TEA), we asked if TEA would inhibit BNC1 with a mutation at residue 430. External TEA blocked BNC1 when residue 430 was a Val or a Thr. Block was steeply voltage-dependent and was reduced when current was outward, suggesting multi-ion block within the channel pore. Block was dependent on the size of the quaternary ammonium; the smaller tetramethylammonium blocked with similar properties, whereas the larger tetrapropylammonium had little effect. When residue 430 was Phe, the effects of tetramethylammonium and tetrapropylammonium were not altered. In contrast, block by TEA was much less voltage-dependent, suggesting that the Phe mutation introduced a new TEA binding site located approximately 30% of the way across the electric field. These results provide insight into the structure and function of BNC1 and suggest that TEA may be a useful tool to probe function of this channel family.  (+info)

RSD1000: a novel antiarrhythmic agent with increased potency under acidic and high-potassium conditions. (3/1462)

This study reports the use of a novel agent, RSD1000 [(+/-)-trans-[2-(4-morpholinyl)cyclohexyl]naphthalene-1-acetate mono hydrochloride], to test the hypothesis that a drug with pKa close to the pH found in ischemic tissue may have selective antiarrhythmic actions against ischemia-induced arrhythmias. The antiarrhythmic ED50 for RSD1000 against ischemic arrhythmias was 2.5 +/- 0.1 micromol/kg/min in rats. This value was significantly lower than doses that suppressed electrically induced arrhythmias. In isolated rat hearts, RSD1000 was approximately 40 times more potent in producing ECG changes (i.e., P-R and QRS prolongation) in acid (pHo = 6.4) and high [K+]o (10.8 mM) buffer than in normal buffer (pHo = 7.4; [K+]o = 3.4 mM). In patch-clamped, whole-cell rat cardiac myocytes, inhibition of sodium (INa) currents by RSD1000 was pH- and use-dependent. The IC50 for INa blockade was lower (P <.05) in acid (0.8 +/- 0.1 microM) than in pH 7.3 (2.9 +/- 0.3 microM), respectively, whereas the IC50 for blockade of transient outward potassium current (ITO) at pH = 6.4 and 7.3 was 3.3 +/- 0.4 and 2.8 +/- 0.1 microM, respectively. Mixed ion channel block in ischemic myocardium with minimal effects on normal cardiac tissue, as governed by the low pKa of RSD1000, may account for its antiarrhythmic activity against ischemia-induced arrhythmias.  (+info)

Cardiac sodium channel Markov model with temperature dependence and recovery from inactivation. (4/1462)

A Markov model of the cardiac sodium channel is presented. The model is similar to the CA1 hippocampal neuron sodium channel model developed by Kuo and Bean (1994. Neuron. 12:819-829) with the following modifications: 1) an additional open state is added; 2) open-inactivated transitions are made voltage-dependent; and 3) channel rate constants are exponential functions of enthalpy, entropy, and voltage and have explicit temperature dependence. Model parameters are determined using a simulated annealing algorithm to minimize the error between model responses and various experimental data sets. The model reproduces a wide range of experimental data including ionic currents, gating currents, tail currents, steady-state inactivation, recovery from inactivation, and open time distributions over a temperature range of 10 degrees C to 25 degrees C. The model also predicts measures of single channel activity such as first latency, probability of a null sweep, and probability of reopening.  (+info)

Calcium block of Na+ channels and its effect on closing rate. (5/1462)

Calcium ion transiently blocks Na+ channels, and it shortens the time course for closing of their activation gates. We examined the relation between block and closing kinetics by using the Na+ channels natively expressed in GH3 cells, a clonal line of rat pituitary cells. To simplify analysis, inactivation of the Na+ channels was destroyed by including papain in the internal medium. All divalent cations tested, and trivalent La3+, blocked a progressively larger fraction of the channels as their concentration increased, and they accelerated the closing of the Na+ channel activation gate. For calcium, the most extensively studied cation, there is an approximately linear relation between the fraction of the channels that are calcium-blocked and the closing rate. Extrapolation of the data to very low calcium suggests that closing rate is near zero when there is no block. Analysis shows that, almost with certainty, the channels can close when occupied by calcium. The analysis further suggests that the channels close preferentially or exclusively from the calcium-blocked state.  (+info)

Distinguishing surface effects of calcium ion from pore-occupancy effects in Na+ channels. (6/1462)

The effects of calcium ion on the Na+ activation gate were studied in squid giant axons. Saxitoxin (STX) was used to block ion entry into Na+ channels without hindering access to the membrane surface, making it possible to distinguish surface effects of calcium from pore-occupancy effects. In the presence of STX, gating kinetics were measured from gating current (Ig). The kinetic effects of external calcium concentration changes were small when STX was present. In the absence of STX, lowering the calcium concentration (from 100 to 10 mM) slowed the closing of Na+ channels (measured from INa tails) by more than a factor of 2. Surprisingly, the voltage sensitivity of closing kinetics changed with calcium concentration, and it was modified by STX. Voltage sensitivity apparently depends in part on the ability of calcium to enter and block the channels as voltage is driven negative. In external medium with no added calcium, INa tail current initially increases in amplitude severalfold with the relief of calcium block, then progressively slows and gets smaller, as calcium diffuses out of the layers investing the axon. INa tails seen just before the current disappears suggest that closing in the absence of channel block is very slow or does not occur. INa amplitude and kinetics are completely restored when calcium is returned. The results strongly suggest that calcium occupancy is a requirement for channel closing and that nonoccupied channels fold reversibly into a nonfunctional conformation.  (+info)

Osmotic regulation of airway reactivity by epithelium. (7/1462)

Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission.  (+info)

N-type calcium channel inactivation probed by gating-current analysis. (8/1462)

N-type calcium channels inactivate most rapidly in response to moderate, not extreme depolarization. This behavior reflects an inactivation rate that bears a U-shaped dependence on voltage. Despite this apparent similarity to calcium-dependent inactivation, N-type channel inactivation is insensitive to the identity of divalent charge carrier and, in some reports, to the level of internal buffering of divalent cations. Hence, the inactivation of N-type channels fits poorly with the "classic" profile for either voltage-dependent or calcium-dependent inactivation. To investigate this unusual inactivation behavior, we expressed recombinant N-type calcium channels in mammalian HEK 293 cells, permitting in-depth correlation of ionic current inactivation with potential alterations of gating current properties. Such correlative measurements have been particularly useful in distinguishing among various inactivation mechanisms in other voltage-gated channels. Our main results are the following: 1) The degree of gating charge immobilization was unchanged by the block of ionic current and precisely matched by the extent of ionic current inactivation. These results argue for a purely voltage-dependent mechanism of inactivation. 2) The inactivation rate was fastest at a voltage where only approximately (1)/(3) of the total gating charge had moved. This unusual experimental finding implies that inactivation occurs most rapidly from intermediate closed conformations along the activation pathway, as we demonstrate with novel analytic arguments applied to coupled-inactivation schemes. These results provide strong, complementary support for a "preferential closed-state" inactivation mechanism, recently proposed on the basis of ionic current measurements of recombinant N-type channels (Patil et al., . Neuron. 20:1027-1038).  (+info)

TY - JOUR. T1 - A sodium channel blocker, pilsicainide, produces atrial post-repolarization refractoriness through the reduction of sodium channel availability. AU - Fukuda, Koji. AU - Watanabe, Jun. AU - Yagi, Takuya. AU - Wakayama, Yuji. AU - Nakano, Makoto. AU - Kondo, Masateru. AU - Kumagai, Koji. AU - Miura, Masahito. AU - Shirato, Kunio. AU - Shimokawa, Hiroaki. PY - 2011/9/2. Y1 - 2011/9/2. N2 - Atrial fibrillation (AF) is the most common tachyarrhythmia. Shortening of atrial action potential duration (APD) and effective refractory period (ERP) is one of the crucial factors in the occurrence and maintenance of AF. ERP is usually shorter than APD, but ERP can be prolonged beyond action potential repolarization in some situations. It is termed as post-repolarization refractoriness (PRR) that is thought to be one of main anti-arrhythmic mechanisms of class I sodium channel blockers (SCBs). Most of anti-arrhythmic agents, including SCBs, have multi-channel blocking effects. It is unknown ...
Dendritic spines mediate most excitatory synapses in the brain. Past theoretical work and recent experimental evidence have suggested that spines could contain sodium channels. We tested this by measuring the effect of the sodium channel blocker tetrodotoxin (TTX) on depolarizations generated by two-photon uncaging of glutamate on spines from mouse neocortical pyramidal neurons. In practically all spines examined, uncaging potentials were significantly reduced by TTX. This effect was postsynaptic and spatially localized to the spine and occurred with uncaging potentials of different amplitudes and in spines of different neck lengths. Our data confirm that spines from neocortical pyramidal neurons are electrically isolated from the dendrite and indicate that they have sodium channels and are therefore excitable structures. Spine sodium channels could boost synaptic potentials and facilitate action potential backpropagation.
A-887826 is a structurally novel, potent and voltage-dependent Na(v)18 sodium channel blocker that attenuates neuropathic tactile allodynia in rats | Laser spine institute london ontariopost_content%%
Topamax (Topiramate) belongs to the group of antiepileptic drugs, which block sodium channels, prevent anxiety and relieve spasms. The medicine is efficient for the treatment of epilepsy, migraine headache and cramps. The drug has spasmolytic, painkilling and anti-inflammatory effect.
Anti arrhythmic drugs are classified into four main classes.. Class I - Sodium channel blockers(act on Phase 0). Class II - Beta blockers(act on phase 4). Class III- Potassium channel blockers(act on phase 3). Class IV - Calcium channel blockers(act on phase 2). ...
Anti arrhythmic drugs are classified into four main classes. Class I - Sodium channel blockers(act on Phase 0) Class II - Beta blockers(act on phase 4) Class III- Potassium channel blockers(act on phase 3) Class IV - Calcium channel blockers(act …. Read more ». ...
Lamictal (Lamotrigine) is a drug that is approved for the treatment of epilepsy and bipolar disorder. It works as a sodium channel blocker by inhibiting vo
Lamictal (Lamotrigine) is a drug that is approved for the treatment of epilepsy and bipolar disorder. It works as a sodium channel blocker by inhibiting vo
Title: Voltage-Gated Sodium Channel Blockers; Target Validation and Therapeutic Potential. VOLUME: 5 ISSUE: 6. Author(s): John N. Wood and James Boorman. Affiliation:Molecular Nociception Group, Biology UCL, Gower Street, London WC1 E 6BT.. Abstract: Voltage-gated sodium channels are encoded by a family of ten structurally-related genes that are expressed in spatially and temporally distinct patterns, mainly in excitable tissues. They underlie electrical signalling in nerve and muscle. It has long been known that sodium channel blockers are anaesthetics as well as powerful analgesics when delivered at low concentrations. In addition, cardiac arrhythmias and epileptic activity can be treated with sodium channel blockers. As we have learned more about the sub-types of sodium channels and their distribution, new therapeutic opportunities have suggested themselves. There are indications that sodium channel blockers may also be useful in affective disorders and schizophrenia. The production of ...
Voltage-gated ion channels allow electrically excitable cells to generate and propagate action potentials and therefore are crucial for nerve and muscle function. Sodium channels play a special role by mediating rapid depolarization, which constitutes the rising phase of the action potential and in turn activates voltage-gated calcium and potassium channels. Voltage-gated sodium channels represent a multigene family. Nine sodium channel subtypes have been cloned and functionally expressed to date. [Clare, J. J., Tate, S. N., Nobbs, M. & Romanes, M. A. Voltage-gated sodium channels as therapeutic targets. Drug Discovery Today 5, 506-520 (2000)]. They are differentially expressed throughout muscle and nerve tissues and show distinct biophysical properties. All voltage-gated sodium channels are characterized by a high degree of selectivity for sodium over other ions and by their voltage-dependent gating. [Catterall, W. A. Structure and function of voltage-gated sodium and calcium channels. Current ...
Class Ib antiarrhythmic agents are sodium channel blockers. They have fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. Class Ib agents shorten the action potential duration and reduce refractoriness. These agents will decrease Vmax in partially depolarized cells with fast response action potentials. They either do not change the action potential duration, or they may decrease the action potential duration. Class Ib drugs tend to be more specific for voltage gated Na channels than Ia. Lidocaine in particular is highly frequency dependent, in that it has more activity with increasing heart rates. This is because lidocaine selectively blocks Na channels in their open and inactive states and has little binding capability in the resting state. Class Ib agents are indicated for the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation. Class Ib ...
Although survival rates of breast, colon and prostate cancers are improving, deaths from these tumors frequently occur due to metastasis. Voltage-gated Na+ channels (VGSCs) are membrane proteins, which regulate membrane current and cellular migration during nervous system organogenesis. VGSCs are also expressed in fibroblasts, immune cells, glia and metastatic cancer cells. VGSCs regulate migration and invasion of breast, bowel and prostate cancer cells, suggesting that they may be novel anti-metastatic targets. We conducted a systematic review of clinical and preclinical studies testing the effects of VGSC-inhibiting drugs in cancer. 204 publications were identified, of which two human, two mouse and 20 in vitro publications were included. In the clinical studies, the effect of these drugs on survival and metastatic relapse is not clear. The 22 preclinical studies collectively suggest that several VGSC-inhibiting drugs inhibit cancer proliferation, migration and invasion. None of the human and only six
LQT3 mutations in the LQTS Registry will be studied using in vitro expression studies to determine whether ranolazine causes a decrease in late sodium current, slower recovery from inactivation and/or changes in time course of inactivation, ameliorating the causative functional effect of each individual mutation.. Individuals with select LQT3 mutations already studied in vitro will be invited to participate in a short term (2 day) study in the Clinical Research Center studying the effects of an oral dose of ranolazine on QTc duration and other ECG, echocardiogram and Holter-derived parameters.. The same individuals, as well as other individuals with the same mutation, will be invited to participate in a 6-month study involving ranolazine and matched placebo, to help evaluate the long-term effectiveness of ranolazine in the population. Periodic ECGs and 24-hour Holter recordings will be obtained for evaluation of QTc duration and other ECG and Holter-derived parameters. ...
Voltage-gated sodium channels play a critical role in the generation and conduction of action potentials - so important for electrical signalling by most excitable cells. Sodium channels are integral membrane proteins and are comprised of a large α subunit, which forms the voltage-sensitive and ion-selective pore, and smaller auxiliary β subunit(s) that can modulate the kinetics and voltage dependence of channel gating. Till 2007, 9 isoforms of the sodium-channel α subunit (Nav1.1- Nav1.9), each with a unique central and peripheral nervous system distribution had been identified. 4 closely related sodium channels (Nav 1.1, -1.2, -1.3, and -1.7) are encoded by a set of 4 genes (SCN1A, SCN2A, SCN3A, and SCN9A, respectively) located within a cluster on chromosome 2q24.3. Mutations in the genes encoding Nav1.1, -1.2, and -1.3 are responsible for a group of epilepsy syndromes with overlapping clinical characteristics but divergent clinical severity, mutation in the gene encoding Nav1.7 has a ...
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... SAN FRANCISCO Jan. 14 2014 /-... Neuropathic pain is estimated to affect more than 20 million people i...,First,Subjects,Dosed,in,Phase,1,Clinical,Study,of,NKTR-171,,A,New,Peripherally-Restricted,Sodium,Channel,Blocker,to,Treat,Neuropathic,Pain,medicine,advanced medical technology,medical laboratory technology,medical device technology,latest medical technology,Health
TY - JOUR. T1 - Sodium channels and pain. AU - Waxman, S. G.. AU - Dib-Hajj, S.. AU - Cummins, T. R.. AU - Black, J. A.. PY - 1999/7/6. Y1 - 1999/7/6. N2 - Although it is well established that hyperexcitability and/or increased baseline sensitivity of primary sensory neurons can lead to abnormal burst activity associated with pain, the underlying molecular mechanisms are not fully understood. Early studies demonstrated that, after injury to their axons, neurons can display changes in excitability, suggesting increased sodium channel expression, and, in fact, abnormal sodium channel accumulation has been observed at the lips of injured axons. We have used an ensemble of molecular, electrophysiological, and pharmacological techniques to ask: what types of sodium channels underlie hyperexcitability of primary sensory neurons after injury? Our studies demonstrate that multiple sodium channels, with distinct electrophysiological properties, are encoded by distinct mRNAs within small dorsal root ...
Definition of sodium channel blocking agent in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is sodium channel blocking agent? Meaning of sodium channel blocking agent as a legal term. What does sodium channel blocking agent mean in law?
Previously cloned voltage-dependent sodium channels exhibit a high degree of homology to one another and appear to comprise a single multigene family. We have now isolated and characterized cDNAs from both human adult heart and fetal skeletal muscle that encode a sodium channel alpha subunit that exhibits only moderate primary structure identity with other sodium channels and is prominently expressed in both heart and uterus. The approximately 7.2-kilobase cDNA sequence, designated hNav2.1, predicts a 1682-amino acid protein that bears 52%, 49%, and 46% overall identity with sodium channels cloned from rat brain, skeletal muscle, and heart, respectively. Positively charged S4 segments are present in hNav2.1, but there are fewer basic residues in repeat domains 1, 3, and 4 than in other cloned sodium channels. The cloning of hNav2.1 provides evidence for greater evolutionary divergence among voltage-dependent sodium channels and suggests that other sodium channel gene subfamilies may exist. The ...
Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with NFASC may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).
Tonic and use-dependent effects of Gd3+ in different conditions, in which blocker potency is altered. Gray lines illustrate traces elicited in the presence of blocker scaled to the magnitude of control currents in the absence of blocker. (A) In 10 mM Ca2+, application of 0.2 μM Gd3+ reduced peak currents by about one half during the first pulse (I1, tonic block), but to a much greater extent at the second pulse (I2, use-dependent block). (B) With 10 mM Ba2+, both tonic and use-dependent block occurred at 25 nM Gd3+. (C) Although Ba2+ currents inactivated more rapidly in channels with the β3 subunit rather than with the β2a subunit (compare with B), tonic and use-dependent effects of Gd3+ were similar for both β subunits. (D) Exemplar Ca2+ currents through the EEQE mutant of the selectivity locus recorded with and without 2 μM Gd3+. (E) Dose-response curves for tonic effect of Gd3+ determined for different experimental conditions (indicated). Tonic block is described by relative magnitude of ...
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Buy Hainantoxin-III, a potent, selective TTX-sensitive voltage-gated Na+ channel blocker. Join researchers using high quality Hainantoxin-III from Abcam and…
TY - JOUR. T1 - Vascular smooth muscle contraction induced by Na+ channel activators, veratridine and batrachotoxin. AU - Shinjo(H), Masayoshi. AU - Toshio, Nakaki. AU - Yukari, Otsuka. AU - Nobuyuki, Sasakawa. AU - Ryuichi, Kato. PY - 1991/11/26. Y1 - 1991/11/26. N2 - The effects of the sodium channel activators veratridine and batrachotoxin on isolated rat aorta were investigated. Veratridine caused gradual contraction, independent of the presence of endolhelium, with an EC50 of 35 μM. Batrachotoxin (1 μM) also induced contraction. Both effects were completely inhibited by the sodium channel blocker tetrodotoxin (1 μM). The veratridine (60 μM)-induced contraction was inhibited by nifedipine (0.1 μM). In the absence of extracellular Ca2+, veratridine (60 μm) did not cause contraction. Sodium nitroprusside (80 nM), acetylcholine (10 μM) and isoproterenol (1 μM) caused relaxation of rings precontracted with veratridine (60 μM). An inhibitor of endothelium-derived relaxing factor (EDRF) ...
Atherton, J. F., Gillies, A. J., Corbett, A. M., & Arbuthnott, G. W. (1998). The Relationship Between Voltage-Gated Sodium Channel Inactivation Firing Frequency in the Subthalamic Nucleus Projection Neuron. European Journal of Neuroscience, 10 (Supplement 10), 300 ...
Scorpion α-toxins LqhαIT, Lqh-2, and Lqh-3 are representatives of three groups of α-toxins that differ in their preference for insects and mammals. These α-insect, antimammalian, and α-like toxins bind to voltage-gated sodium channels and slow down channel inactivation. Sodium channel mutagenesis studies using various α-toxins have shown that they interact with receptor site 3, which is composed mainly of a short stretch of amino-acid residues between S3 and S4 of domain 4. Variation in this region results in marked differences between various subtypes of sodium channels with respect to their sensitivity to the three Lqh toxins. We incorporated the S3-S4 linker of domain 4 from hNaV1.2/hNaV1.1, hNaV1.3, hNaV1.6, and hNaV1.7 channels as well as individual point mutations into the rNaV1.4 skeletal muscle sodium channel. Our data show that the affinity of Lqh-3 and LqhαIT to sodium channels is markedly determined by an aspartate residue (Asp1428 in rNaV1.4); when mutated to glutamate, as is ...
WEDNESDAY, Nov. 27, 2019 (HealthDay News) -- Millions of Americans have the potentially dangerous irregular heartbeat known as atrial fibrillation.. Now, research suggests that being obese might undercut the effectiveness of certain drugs meant to treat AFib.. The new study followed more than 300 patients listed in the University of Illinois at Chicagos AFib Registry. Researchers found that a class of medicines called sodium channel blockers, which are often used to treat AFib, were less effective in obese patients. In fact, the recurrence rate for the heart arrhythmia was 30% for obese patients taking sodium channel blockers, compared with 6% for non-obese patients. That could be bad news for many patients, since obesity is a big risk factor for AFib, said a team led by Dr. Dawood Darbar, head of cardiology at the universitys College of Medicine. Still, obese patients may have a viable option: Darbars team found that another class of drugs, called potassium channel blockers, worked better in ...
Voltage-gated sodium channels are important targets for the development of pharmaceutical drugs, because mutations in different human sodium channel isoforms have causal relationships with a range of neurological and cardiovascular diseases. In this study, functional electrophysiological studies show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds and is inhibited by eukaryotic sodium channel blockers in a manner similar to the human Nav1.1 channel, despite millions of years of divergent evolution between the two types of channels. Crystal complexes of the NavMs pore with several brominated blocker compounds depict a common antagonist binding site in the cavity, adjacent to lipid-facing fenestrations proposed to be the portals for drug entry. In silico docking studies indicate the full extent of the blocker binding site, and electrophysiology studies of NavMs channels with mutations at adjacent residues validate the location. These results suggest that the NavMs ...
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The potassium-sparing diuretics are competitive antagonists that either compete with aldosterone for intracellular cytoplasmic receptor sites, or directly block sodium channels (specifically epithelial sodium channels (ENaC) by amiloride ). The
The octopus produces venom that contains tetrodotoxin, 5-hydroxytryptamine, hyaluronidase, tyramine, histamine, tryptamine, octopamine, taurine, acetylcholine, and dopamine. The major neurotoxin component of Blue-ringed Octopus venom was originally known as maculotoxin, but was later found to be identical to tetrodotoxin, a neurotoxin which is also found in pufferfish and cone snails. Tetrodotoxin blocks sodium channels, causing motor paralysis and sometimes respiratory arrest leading to cardiac arrest due to a lack of oxygen. The toxin is created by bacteria in the salivary glands of the octopus ...
The octopus produces venom containing tetrodotoxin, 5-hydroxytryptamine, hyaluronidase, tyramine, histamine, tryptamine, octopamine, taurine, acetylcholine, and dopamine. The major neurotoxin component of blue-ringed octopus venom was originally known as maculotoxin but was later found to be identical to tetrodotoxin, a neurotoxin also found in pufferfish and some poison dart frogs that is 10,000 times more toxic than cyanide. Tetrodotoxin blocks sodium channels, causing motor paralysis and respiratory arrest within minutes of exposure, leading to cardiac arrest due to a lack of oxygen. The toxin is produced by bacteria in the salivary glands of the octopus. Their venom can result in nausea, respiratory arrest, heart failure, severe and sometimes total paralysis and blindness and can lead to death within minutes if not treated. Death is usually from suffocation due to lack of oxygen to the brain ...
Voltage-gated sodium channels, which initiate action potentials in mammalian brain neurons, are modulated functionally by cAMP-dependent protein kinase A (PKA), resulting in reduced sodium current amplitude. Comparing brain and muscle sodium channels, we show that only the brain channel is modulated by PKA. The brain sodium channel I-II linker is both necessary and sufficient for PKA modulation, as shown by exchanging the I-II linker regions of the two channels. PKA consensus sites in the brain channel I-II linker were eliminated by deletion and site-specific mutagenesis. The mutant channels demonstrated decreased levels of phosphorylation when metabolically labeled in oocytes with [gamma-32P]-ATP, and they did not respond with a reduction in current magnitude after PKA induction. Modulation of the brain channel by PKA phosphorylation was mimicked by adding fixed negative charges at the PKA consensus sites, suggesting that the decrease in current was a direct result of the negative charge at one ...
Activyl® contains indoxacarb, an active ingredient with an innovative mode of action for flea control. Indoxacarb acts as a highly potent sodium channel blocker to impede insect nerve impulse transmission. Fleas stop feeding, become paralyzed and die. Activyl® is adulticidal, larvicidal and inhibits flea development in the environment. Features: ...
1 . Platkiewicz J, Brette R (2011) Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. PLoS Comput Biol 7:e1001129-78 [PubMed] ...
Strupp, Michael; Quasthoff, Stefan; Mitrović, N. und Grafe, Peter (1992): Glutathione accelerates sodium channel inactivation in excised rat axonal membrane patches. In: Pflügers Archiv European Journal of Physiology, Vol. 421, Nr. 2-3: S. 283-285 [PDF, 349kB] ...
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Lubeluzole is widely reported as a multitarget drug acting at least on voltage-gated calcium and sodium channels. There are, however, only a very few studies reporting direct demonstration of sodium channel blockade by lubeluzole in neuronal and cardiac cells (Osikowska-Evers et al., 1995; Le Grand et al., 2003). The more complete study by Le Grand et al., (2003) described the block of sodium channels in single guinea pig ventricular myocytes. It was shown that lubeluzole produces a concentration-dependent tonic and use-dependent block of cardiac sodium channels in a manner similar to that of class I antiarrhythmic drugs, suggesting a greater affinity for inactivated than for resting channels. In the present study, we observed a similar local anesthetic-like effect of lubeluzole on human skeletal muscle sodium channels, and definitely demonstrated that the drug is a very potent blocker of inactivated sodium channels compared with resting channels. The IC50 values calculated for skeletal muscle ...
The present invention pertains to the field of compounds having sodium ion channel blocking activity, a process for preparing the same and use thereof. Previously described compounds targeting this activity have had issues including poor selectivity and/or potency, and in some cases, are not effective for some types of pain. The present invention addresses these issues by the provision of a compound represented by Chemical Formula 1 (shown) or a pharmaceutically acceptable salt thereof, which may be useful for the prevention or treatment of sodium channel blocker-related diseases such as acute pain, chronic pain, neuropathic pain, postoperative pain, migraine, arthralgia, neuropathy, nerve damage, diabetic neuropathy, neuropathic disease, epilepsy, arrhythmia, myotonia, ataxia, multiple sclerosis, irritable bowel syndrome, urinary incontinence, visceral pain, depression, erythralgia, or PEPD (paroxysmal extreme pain disorder).
AIMS: Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors of ajmaline-induced PR and QRS changes and Type I Brugada syndrome (BrS) electrocardiogram (ECG). METHODS AND RESULTS: In 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements of 26 721 ECGs, dose-response mixed modelling and genotyping. We calculated polygenic risk scores (PRS) for PR interval (PRSPR), QRS duration (PRSQRS), and Brugada syndrome (PRSBrS) derived from published genome-wide association studies and used regression analysis to identify predictors of ajmaline dose related PR change (slope) and QRS slope. We derived and validated using bootstrapping a predictive model for ajmaline-induced Type I BrS ECG. Higher PRSPR, baseline PR, and female sex are associated with more pronounced PR slope, while PRSQRS and age are positively associated with QRS slope (P , 0.01 for all). PRSBrS, ...
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TY - JOUR. T1 - Voltage-dependent sodium channel function is regulated through membrane mechanics. AU - Shcherbatko, Anatoly. AU - Ono, Fumihito. AU - Mandel, Gail. AU - Brehm, Paul. PY - 1999/10. Y1 - 1999/10. N2 - Cut-open recordings from Xenopus oocytes expressing either nerve (PN1) or skeletal muscle (SkM1) Na+ channel α subunits revealed slow inactivation onset and recovery kinetics of inward current. In contrast, recordings using the macropatch configuration resulted in an immediate negative shift in the voltage-dependence of inactivation and activation, as well as time-dependent shifts in kinetics when compared to cut-open recordings. Specifically, a slow transition from predominantly slow onset and recovery to exclusively fast onset and fast recovery from inactivation occurred. The shift to fast inactivation was accelerated by patch excision and by agents that disrupted microtubule formation. Application of positive pressure to cell-attached macropatch electrodes prevented the shift in ...
Arrhythmias arise from breakdown of orderly action potential (AP) activation, propagation and recovery driven by interactive opening and closing of successive voltage-gated ion channels, in which one or more Na+ current components play critical parts. Early peak, Na+ currents (I Na) reflecting channel activation drive the AP upstroke central to cellular activation and its propagation. Sustained late Na+ currents (I Na-L) include contributions from a component with a delayed inactivation timecourse influencing AP duration (APD) and refractoriness, potentially causing pro-arrhythmic phenotypes. The magnitude of I Na-L can be analysed through overlaps or otherwise in the overall voltage dependences of the steady-state properties and kinetics of activation and inactivation of the Na+ conductance. This was useful in analysing repetitive firing associated with paramyotonia congenita in skeletal muscle. Similarly, genetic cardiac Na+ channel abnormalities increasing I Na-L are implicated in triggering
This paper shows that persistent sodium current critically contributes to the subthreshold nonlinear dynamics of CA1 pyramidal neurons and promotes rapidly reversible conversion between place-cell and silent-cell in the hippocampus. A simple model built with realistic axo-somatic voltage-gated sodium channels in CA1 (Carter et al., 2012; Neuron 75, 1081-1093) demonstrates that the biophysics of persistent sodium current is sufficient to explain the synaptic amplification effects. A full model built previously (Grienberger et al., 2017; Nature Neuroscience, 20(3): 417-426) with detailed morphology, ion channel types and biophysical properties of CA1 place cells naturally reproduces the steep voltage dependence of synaptic responses ...
In the present work, we improve this model neuron by including morphological details. We take the morphological information from identified larval aCC abdominal dorsomedial motoneurons, which innervate the dorsal muscles [4]. A two-compartment version of the model is used to assess effects of changing sodium channel properties. This neuron model allows investigating the effect of sodium channel splice variants by varying half-activation and inactivation voltages and ratio of a persistent component to mimic changes observed in sodium channel current properties in seizure mutants. We further analyze the effect that changes in synaptic input observed in seizure mutants have on the output neuronal activity. ...
In this study, we found that focal injection of the sodium channel blocker TTX into the injury site after a standardized spinal cord contusion dramatically reduced acute WM pathology. Specifically, TTX significantly attenuated the loss of large (≥5 μm)-diameter axons. The surviving axons in the TTX group demonstrated less axoplasmic pathology in comparison to those in the VEH group. The effectiveness of TTX appears to be in its ability to reduce axonal pathology per se as opposed to reducing injury-induced loss of glia or myelin pathology after SCI.. We previously showed that focal microinjection of TTX (0.15 nmol) into the lesion site significantly reduced WM loss at the injury epicenter chronically at 8 weeks after SCI (Teng and Wrathall, 1997). Morphometry analysis showed a three-fold sparing of WM in the TTX-treated group compared with VEH controls. This led us to hypothesize that TTX treatment was sparing axons. The finding that TTX treatment spared large axons is particularly ...
Procaine. Molecular model of the local anaesthetic drug procaine (C13.H20.N2.O2), also known as novocaine. This drug acts as a sodium channel blocker. Atoms are represented as spheres and are colour-coded: carbon (grey), hydrogen (white), nitrogen (blue) and oxygen (red). Illustration. - Stock Image F017/0546
Shop Sodium channel and clathrin linker ELISA Kit, Recombinant Protein and Sodium channel and clathrin linker Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
The ATP-binding cassette, subfamily G, isoform 2 protein (ABCG2) is a vital member of the ABC transporter superfamily, which has been involved in multidrug resistance (MDR) in cancer. Its diverse range of substrates includes many antineoplastic agents such as doxorubicin and mitoxantrone. ABCG2 expression has been significantly increased in some solid tumors and hematologic malignancies, which is correlated to poorer clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membranous transporter imparts resistance to the chemotherapeutic drugs. To enhance the chemosensitivity of cancer cells, attention has been focused on MDR modulators. In this study, we investigated the ability of sodium channel blocker, A-803467 to reverse ABCG2-mediated MDR. We found that A-803467 at non-toxic concentration could significantly increase the cellular sensitivity to ABCG2 substrates in drug-resistant cells overexpressing either wild-type or mutant ABCG2. ...
A cross-section of an axon, with an action potential (AP) moving from left to right. The AP has not yet reached point 4; the membrane there is still at rest. At point 3, positive sodium ions are moving in from the adjacent region, depolarizing the region; the sodium channels are about to open. Point 2 is at the peak of the AP; the sodium channels are open and ions are flowing into the axon. The AP has passed by point 1; the sodium channels are inactivated, and the membrane is hyperpolarized ...
Epithelial sodium channel blockers: amiloride and triamterene.. Calcium-sparing diuretics[edit]. The term "calcium-sparing ... Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels[16] 5 ... Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. ... This is large in comparison to normal renal sodium reabsorption which leaves only about 0.4% of filtered sodium in the urine. ...
Certain anticonvulsant drugs that are classed as Sodium Channel Blockers are now known to make seizures worse in most Dravet ... "SCN1A Patients Advised to Avoid Sodium Channel Blockers". Retrieved 1 January 2016.. ... a missense mutation in either the S5 or S6 segment of the sodium channel pore results in a loss of channel function and the ... Cheah, C; Catterall, W.A. (2012). "Characterizing the role of sodium channels in mouse models of Dravet Syndrome".. ,access- ...
... is a sodium channel blocker.[28] It binds preferentially to voltage-gated sodium channels in their inactive ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, ... and calcium channel blockers.[12] Carbamazepine also increases the metabolism of the hormones in birth control pills and can ... "Sodium valproate versus phenytoin monotherapy for epilepsy: an individual participant data review". The Cochrane Database of ...
It acts mainly as a sodium channel blocker.[1] Today it is used therapeutically in some countries due to its sympatholytic, ... consists of the direct reaction of the 4-aminobenzoic acid ethyl ester with 2-diethylaminoethanol in the presence of sodium ...
Static mechanical allodynia - sodium channel blockers, opioids. *Lidocaine (IV). *Alfentanil (IV). *Adenosine (IV) ...
... is a class 1a antiarrhythmic agent; a sodium channel blocker. It is an alkaloid and can be extracted from scotch ... thus is can be assumed that the enzyme catalyzes the formation of the quinolizidine skeleton in a channeled fashion (Figure 2 ...
Sodium channel blocker. ... down electrical signaling in nerves by blocking sodium channels ...
... is chemically similar to pyrazoline sodium channel blocker insecticides (SCBIs) discovered at Philips-Duphar in ... PetPlace Drug Library Salgado, VL; Hayashi, JH (2007). "Metaflumizone is a novel sodium channel blocker insecticide". ... Metaflumizone blocks sodium channels by binding selectively to the slow-inactivated state, which is characteristic of the SCBIs ... Metaflumizone works by blocking sodium channels in target insects, resulting in paralyzation associated with blocking nerve ...
Remacemide: a low affinity antagonist also a sodium-channel blocker. Delucemine: also a SSRI with neuroprotective properties. ... An NMDA receptor that has glycine and glutamate bound to it and has an open ion channel is called "activated." Chemicals that ... Aptiganel (Cerestat, CNS-1102): binds the Mg2+ binding site within the channel of the NMDA receptor. HU-211: an enantiomer of ... AZD6765 Agmatine: Blocks NMDA receptors and other cation ligand-gated channels. Can also potentiate opioid analgesia. ...
All of the peptides are voltage-gated sodium channel blockers. To date, Aps III is known to be the most potent peptide of all. ... "The insecticidal neurotoxin Aps III is an atypical knottin peptide that potently blocks insect voltage-gated sodium channels". ...
... (INN) (developmental code names NW-3509, NW-3509A) is a selective voltage-gated sodium channel blocker, including ( ... "Advances in Design and Development of Sodium Channel Blockers": 79-115. doi:10.1007/978-3-642-19922-6_4. http://labiotech.eu/ ... 81-. ISBN 978-0-12-381293-3. Satya Prakash Gupta (21 June 2011). Ion Channels and Their Inhibitors. Springer Science & Business ...
... either spontaneously present or induced with the sodium channel-blocker challenge test, is considered diagnostic. Type 2 and 3 ... Some are responsible for other proteins that form part of the sodium channel, known as sodium channel β subunits (SCN1B, SCN2B ... NaV1.5 - α subunit of the cardiac sodium channel carrying the sodium current INa.[6] ... NaVβ3 - β-3 subunit of the cardiac sodium channel carrying the sodium current INa.[6] ...
"Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers". Nature. 449 (7162): 607-610. doi: ... channel activity confers resistance to epileptic seizures". Neuron. 74 (4): 719-730. doi:10.1016/j.neuron.2012.03.032. ISSN ... "for structural and mechanistic studies of ion channels" 2004: Linda Buck (faculty member 1991-2001) "for...discoveries of ... and nonhuman primates Ion channel physiology Neurobiology of Behavior Neurodevelopmental disorders, such as Rett Syndrome and ...
... is a sodium channel blocker. It binds preferentially to voltage-gated sodium channels in their inactive ... and calcium channel blockers. Carbamazepine also increases the metabolism of the hormones in birth control pills and can reduce ...
Sodium channel blockers directly inhibit the entry of sodium into the sodium channels. Common side effects may include a ... Triamterene directly blocks the epithelial sodium channel (ENaC) on the lumen side of the kidney collecting tubule. Other ... diuretics cause a decrease in the sodium concentration of the forming urine due to the entry of sodium into the cell via the ... September 1996). "Blockade of epithelial Na+ channels by triamterenes - underlying mechanisms and molecular basis". Pflugers ...
... acts as a blocker of voltage-gated sodium channels. Inhibition of the Nav1.5 channel is specifically involved in its ... Rapid Interpretation of EKG's 6th Ed., Dubin de Lera Ruiz M, Kraus RL (2015). "Voltage-Gated Sodium Channels: Structure, ... Hugues Abriel (1 September 2015). Cardiac Sodium Channel Disorders, An Issue of Cardiac Electrophysiology Clinics, E-Book. ... The effect of quinidine on the ion channels is to prolong the cardiac action potential, thereby prolonging the QT interval on ...
Class I agents are sodium (Na) channel blockers (which slow conduction by blocking the Na+ channel) and are divided into 3 ... acts to promote influx of sodium through slow-sodium channels). It has been shown to be effective in acute cardioversion of ... Class IV drugs are calcium (Ca) channel blockers. They work by inhibiting the action potential of the SA and AV nodes. ... Not all beta blockers are the same; some are cardio selective (affecting only beta 1 receptors) while others are non-selective ...
It acts as a small-molecule Nav1.7 and Nav1.8 voltage-gated sodium channel blocker. Funapide is being evaluated in humans in ... "Recent progress in sodium channel modulators for pain". Bioorganic & Medicinal Chemistry Letters. 24 (16): 3690-9. doi:10.1016/ ...
Site 1 binds the sodium channel blockers tetrodotoxin and saxitoxin. Site 2 binds lipid-soluble sodium channel activators such ... Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family. Sodium-channel ... which slow sodium channel inactivation. Site 4 binds beta-scorpion toxins, which affect sodium channel activation. Site 5 binds ... "A new neurotoxin receptor site on sodium channels is identified by a conotoxin that affects sodium channel inactivation in ...
"Chronic Exposure to NMDA Receptor and Sodium Channel Blockers during Development in Monkeys and Rats". Annals of the New York ... Remacemide is a drug which acts as a low-affinity NMDA antagonist with sodium channel blocking properties. It has been studied ... Santangeli, Sarah; Sills, Graeme J; Thompson, George G; Brodie, Martin J (1 March 2002). "Na+ channel effects of remacemide and ... Remacemide binds weakly and noncompetitively to the ionic channel site of the NMDA receptor complex. Remacemide binds both ...
Arothron mappa contains tetrodotoxin - an extremely toxic sodium channel blocker which protects it from predators. http://www. ...
"A naturally-occurring carboxyl-terminally truncated α-scorpion toxin is a blocker of sodium channels". Biochemical and ... but showed no effects on various other potassium channels tested. Inhibitors of sodium channels have also been found in this ... Gao, B; Peigneur, S; Tytgat, J; Zhu, S (2010). "A potent potassium channel blocker from Mesobuthus eupeus scorpion venom". ... In contrast, BeKm-1 specifically inhibits hERG channels, which are potassium channels critical to maintaining normal electrical ...
Structure--activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers ... and HNTX-V are thought to bind to site 1 of voltage-dependent sodium channels, similar to TTX, and thereby block the channel ... voltage-gated sodium channels (VGSCs). Voltage-gated Ca2+ channels (VGCCs), tetrodotoxin-resistant (TTX-R) VGSCs and rectifier- ... Inhibition of sodium channels in rat dorsal root ganglion neurons by Hainantoxin-IV, a novel spider toxin. Sheng Wu Hua Xue Yu ...
"The efficacy of sodium channel blockers to prevent phencyclidine-induced cognitive dysfunction in the rat: potential for novel ... Phencyclidine enters the ion channel and binds, reversibly and non-competitively, inside the channel pore to block the entry of ... when activated normally the receptor acts as an ion channel and there is an influx of positive ions through the channel to ... Interaction of phencyclidine and its analogues on ionic channels of the electrically excitable membrane and nicotinic receptor ...
Tetrodotoxin, a sodium channel blocker, can be administered to suppress the prolonged action potential. Ca2+-channel blockers ( ... one acting on sodium channels and one acting on calcium channels . The toxin acting on Na+ channels has a molecular weight of ... The 19 kDa GPT stimulates Ca2+ influx and its activity can be prevented in the presence of a calcium channel blocker. This ... In guinea-pig ventricular cells, the 12 kDa GPT prolonged the action potential by acting on sodium channels, again with no ...
But if the γ2 is expressed with α1 and β2 the sensitivity is low and channel conductance is high.[7] γ2 subunit has to be ... Bromide compounds (e.g., lithium bromide, potassium bromide, sodium bromide). *Carbamazepine. *Chloralose ... Upon binding, it triggers the GABAA receptor to open its chloride channel to allow chloride ions into the neuron, making the ... The channel conductance is not higher in the presence of benzodiazepine and GABA than the conductance with the presence of only ...
Current clinical available anti-epileptics are mostly sodium channel blockers. The sodium channel blockers were very effective ... 4a). Similarly, when the cells were treated with TTX, a specific sodium channel blocker, or BKCa channel activator NS1619 (5 μM ... Being a positive control, TTX, a voltage-gated sodium channel blocker, significantly reduced sodium current amplitude (Fig. 3a ... ResveratrolBKCa channelSodium channelAction potentialFiring rate. Background. Resveratrol (trans-3,4,5-trihydroxystilbene), a ...
6 The sodium channel blocker tetrodotoxin (TTX; 1 mu M) abolished the relaxations of the rabbit isolated corpus cavernosum ... Similarly, the Kt channel blocker tetraethylammonium (TEA; 10 mu M) had no effect on the venom-induced relaxations. 5 Capsaicin ... The ATP-dependent K+ channel antagonist glibenclamide (10 mu M) and the Ca2+-activated K+ channel antagonists apamin (0.1 mu M ...
The calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicity. Science. 1990;247:1474-1477. ... an antagonist of voltage-sensitive sodium channels). These data suggest that the relative contribution of glutamate receptor ... The neuroprotective activity of specific L-type channel blockers is equivocal, with numerous positive and negative reports.5 6 ... Treatment with conotoxin, an N-type calcium channel blocker, in neuronal hypoxic-ischemic injury. Brain Res. 1990;537:256-262 ...
Sodium channel blockers are drugs which impair the conduction of sodium ions (Na+) through sodium channels.[1] ... Sodium channel opener. References[edit]. *^ Sodium+Channel+Blockers at the US National Library of Medicine Medical Subject ... sodium channels.[3]. Antiarrhythmic[edit]. Sodium channel blockers are used in the treatment of cardiac arrhythmia. They are ... "Sodium channel blockers for cystic fibrosis".. *^ Dick IE, Brochu RM, Purohit Y, Kaczorowski GJ, Martin WJ, Priest BT (April ...
a zip file of the full study records in XML for all studies in the search results table (max 10000 ...
WebMD provides information about interactions between Stavzor Oral and sodium-channel-blocker-potassium-channel-blocker- ... Lacosamide/Sodium Channel Blockers; Potassium Channel Blockers Interactions. This information is generalized and not intended ...
A sodium channel blocker is a medication that is used to correct abnormal heart rhythms by affecting the electrical impulses ... A sodium channel blocker is a medication that is categorized as a Class I antiarrhythmic drug. This means that it works to ... Typically, a sodium channel blocker may cause dizziness, nausea, and vomiting, along with diarrhea or constipation. Loss of ... People taking a sodium channel blocker may experience some side effects, which should be reported to the prescribing physician ...
Efficacy Study of Sodium Channel Blocker in LQT3 Patients. This study is currently recruiting participants. See Contacts and ... The purpose of this study is to determine whether late sodium channel blockade might be effective in shortening the QTc ... In vitro studies of specific mutation show no effect of ranolazine on late sodium current kinetics or show repolarization ... Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J ...
An epithelial sodium channel blocker is a sodium channel blocker that is selective for the epithelial sodium channel. An ... Sagnella GA, Swift PA (2006). "The renal epithelial sodium channel: genetic heterogeneity and implications for the treatment of ...
... which may be useful for the prevention or treatment of sodium channel blocker-related diseases such as acute pain, chronic pain ... The present invention pertains to the field of compounds having sodium ion channel blocking activity, a process for preparing ... NZ742069A - Sodium channel blocker - Google Patents. Sodium channel blocker Info. Publication number. NZ742069A. NZ742069A ... Benzaepinones as sodium channel blockers WO2008075353A1 (en) * 2006-12-19. 2008-06-26. Pharmos Corporation. Sulfonamide ...
Selective sodium channel blockers in trigeminal neuralgia Selective sodium channel blockers in trigeminal neuralgia. Research ... Selective sodium channel blockers in trigeminal neuralgia. / Jensen, Troels Staehelin.. In: Lancet Neurology, Vol. 16, No. 4, ... "Selective sodium channel blockers in trigeminal neuralgia". Lancet Neurology. 2017, 16(4). 255-256. Available: 10.1016/S1474- ... Selective sodium channel blockers in trigeminal neuralgia. Lancet Neurology. 2017 Apr;16(4):255-256. Available from, DOI: ...
The National Center for Biomedical Ontology was founded as one of the National Centers for Biomedical Computing, supported by the NHGRI, the NHLBI, and the NIH Common Fund under grant U54-HG004028 ...
A-803467, a sodium channel blocker, reverses ABCG2-mediated MDR. [abstract]. In: Proceedings of the 105th Annual Meeting of the ... In this study, we investigated the ability of sodium channel blocker, A-803467 to reverse ABCG2-mediated MDR. We found that A- ... Abstract 1967: A-803467, a sodium channel blocker, reverses ABCG2-mediated MDR. Nagaraju Anreddy ... Abstract 1967: A-803467, a sodium channel blocker, reverses ABCG2-mediated MDR ...
To further explore the roles of NMDA receptors and sodium channels in these effects, MK-801, phenytoin (sodium channel blocker ... Chronic exposure to NMDA receptor and sodium channel blockers during development in monkeys and rats: long-term effects on ... The effects of chronic administration of MK-801 (NMDA-receptor antagonist) and remacemide (sodium channel blocker) on monkey ... In the rat, blockade of sodium channels was well tolerated but blockade of NMDA receptors had significant and long-term ( ...
Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord ... Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord ... Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord ... Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord ...
Interaction between selected sodium and potassium channel blockers in guinea pig papillary muscle.. L Wang, N Chiamvimonvat and ... Interaction between selected sodium and potassium channel blockers in guinea pig papillary muscle.. L Wang, N Chiamvimonvat and ... Interaction between selected sodium and potassium channel blockers in guinea pig papillary muscle.. L Wang, N Chiamvimonvat and ... Interaction between selected sodium and potassium channel blockers in guinea pig papillary muscle. ...
NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.. [K J Coote, ... Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis ( ... The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in ... Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal ...
Sodium,Channel,Blocker,to,Treat,Neuropathic,Pain,medicine,advanced medical technology,medical laboratory technology,medical ... A peripherally-restricted sodium channel blocker with good efficacy and low CNS side effects would be an important advance in ... The sodium channel blocker lidocaine is known to be effective in addressing peripheral nerve pain, however it is not selective ... "While conventional sodium channel blockers have demonstrated efficacy in addressing peripheral nerve pain, the CNS-mediated ...
... showed attenuation of ER in inferior or lateral leads by sodium channel blocker infusion (94%). Comparing to patients in BS ... provocative tests with sodium-channel blockers were performed in all ERS and BS patients. ... early repolarization in inferior or lateral leads in both ERS and BS patients were attenuated by sodium channel blocker ... of Idiopathic Ventricular Fibrillation with Early Repolarization and Response of Early Repolarization to Sodium Channel Blocker ...
WB4101 as a Sodium Channel Blocker. Min Li, Ying Wu, Beiyan Zou, Xiaoliang Wang, Min Li and Haibo Yu ... WB4101 as a Sodium Channel Blocker. Min Li, Ying Wu, Beiyan Zou, Xiaoliang Wang, Min Li and Haibo Yu ... Identification of WB4101, an α1-Adrenoceptor Antagonist, as a Sodium Channel Blocker. Min Li, Ying Wu, Beiyan Zou, Xiaoliang ... In conclusion, the present study identified WB4101 as a sodium channel blocker with an open-state-dependent property, which may ...
A selective Nav1.8 sodium channel blocker, A-803467, attenuates spinal neuronal activity in neuropathic rats. Steve McGaraughty ... A selective Nav1.8 sodium channel blocker, A-803467, attenuates spinal neuronal activity in neuropathic rats. Steve McGaraughty ... A selective Nav1.8 sodium channel blocker, A-803467, attenuates spinal neuronal activity in neuropathic rats. Steve McGaraughty ... A selective Nav1.8 sodium channel blocker, A-803467, attenuates spinal neuronal activity in neuropathic rats ...
... although the properties of naturally occurring toxin blockers suggest that subtype-specific blockers of sodium channels could ... although the properties of naturally occurring toxin blockers suggest that subtype-specific blockers of sodium channels could ... Voltage-Gated Sodium Channel Blockers; Target Validation and Therapeutic Potential. Author(s): John N. Wood, James Boorman. ... It has long been known that sodium channel blockers are anaesthetics as well as powerful analgesics when delivered at low ...
Site-1 Sodium Channel Blockers as Local Anesthetics: Will Neosaxitoxin Supplant the Need for Continuous Nerve Blocks?. ... Site-1 Sodium Channel Blockers as Local Anesthetics: Will Neosaxitoxin Supplant the Need for Continuous Nerve Blocks? ... Site-1 Sodium Channel Blockers as Local Anesthetics: Will Neosaxitoxin Supplant the Need for Continuous Nerve Blocks? ... Laura A. Lahaye, John F. Butterworth; Site-1 Sodium Channel Blockers as Local Anesthetics: Will Neosaxitoxin Supplant the Need ...
Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the ... 3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na(V)1.7 with Efficacy in Rat ... The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic ...
P-321, a Novel Long-Acting Epithelial Sodium Channel (ENaC) Blocker for the Treatment of Dry Eye Disease ... P-321, a Novel Long-Acting Epithelial Sodium Channel (ENaC) Blocker for the Treatment of Dry Eye Disease ... a Novel Long-Acting Epithelial Sodium Channel (ENaC) Blocker for the Treatment of Dry Eye Disease. Invest. Ophthalmol. Vis. Sci ... Keywords: 486 cornea: tears/tear film/dry eye • 475 conjunctivitis • 569 ion channels ...
  • Moreover, the effects of resveratrol on action potential firing rate and the BK Ca channel inhibitor TEA (or paxilline)-induced hyperexcitability were also evaluated. (biomedcentral.com)
  • In this study, the interactions between the prolongation of action potential duration (APD) by a potassium channel blocker and the reduction in the maximal upstroke velocity of phase 0 of action potential (Vmax) by sodium channel blockers were investigated in guinea pig papillary muscle using conventional microelectrode techniques. (aspetjournals.org)
  • However, use of capsaicin as the activator of TRPV1 channels would likely lead to an intense, if short-lasting, pain before the impermeant sodium channel blocker entered the nociceptors in sufficient quantities to interrupt conduction, limiting clinical application. (asahq.org)
  • The ability to inactivate is thought to be due to a tethered plug (formed by domains III and IV of the alpha subunit), called an inactivation gate, that blocks the inside of the channel shortly after it has been activated. (bionity.com)
  • Expression of the alpha subunit alone is sufficient to produce a functional channel. (wikidoc.org)
  • Further, the state-dependent inhibition on sodium channels induced by WB4101 was demonstrated in dorsal root ganglion neurons. (aspetjournals.org)
  • CB1R is ubiquitously expressed on neurons throughout the central nervous system primarily at pre-synaptic sites, and is activated by the endocannabinoids AEA or 2-AG to decrease the probability of neurotransmitter release through inhibition of voltage-dependent calcium channels or activation of inwardly rectifying potassium channels ( Wilson and Nicoll, 2002 ). (frontiersin.org)
  • Chronic exposure to NMDA receptor and sodium channel blockers during development in monkeys and rats: long-term effects on cognitive function. (sigmaaldrich.com)
  • To further explore the roles of NMDA receptors and sodium channels in these effects, MK-801, phenytoin (sodium channel blocker), or both were administered to rats and the acquisition of tasks similar to those used in the monkey study were assessed. (sigmaaldrich.com)
  • Turning off the light or irradiating the cells with green light alters the shape of the compound in such a way that the block is released and sodium ions flow through the channel pore into the cell. (phys.org)
  • While conventional sodium channel blockers have demonstrated efficacy in addressing peripheral nerve pain, the CNS-mediated side effects associated with these medicines make the treatment intolerable for many patients. (bio-medicine.org)
  • Targeting membrane-impermeant polar local anesthetics specifically into pain fibers by activation of nociceptive-specific transducer channels could be used clinically to produce a long-lasting nociceptive-selective block while preserving motor and autonomic function-a regional analgesia. (asahq.org)
  • Results of pH-dependence experiments led to the proposal of two alternative access pathways for local anesthetics to their binding site, a hydrophobic pathway through the membrane phase, and a hydrophilic pathway for the charged form of the molecules from the intracellular side of the membrane, through the activation gate of the channel. (frontiersin.org)
  • The α-subunit forms ion-conducting aqueous pore whereas auxiliary β subunits modify the kinetics and voltage-dependence of channel gating. (duhnnae.com)
  • Sodium channel blockers have been proposed for use in the treatment of cystic fibrosis, but current evidence is mixed. (wikipedia.org)
  • Sodium channel blockers for cystic fibrosis: Cochrane systematic review is a topic covered in the Cochrane Abstracts . (unboundmedicine.com)
  • Cochrane Abstracts , Evidence Central , evidence.unboundmedicine.com/evidence/view/Cochrane/431700/all/Sodium_channel_blockers_for_cystic_fibrosis:_Cochrane_systematic_review. (unboundmedicine.com)