A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Ion channels 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.
Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.
An 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.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.
A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
A 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.
A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11.
A voltage-gated sodium channel subtype found widely expressed in neurons of the central and peripheral nervous systems. Defects in the SCN8A gene which codes for the alpha subunit of this sodium channel are associated with ATAXIA and cognitive deficits.
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.
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.
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.
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.
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.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.
A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.
A voltage-gated sodium channel subtype that is expressed in nociceptors, including spinal and trigeminal sensory neurons. It plays a role in the transmission of pain signals induced by cold, heat, and mechanical stimuli.
A class of drugs that stimulate sodium influx through cell membrane channels.
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.
Morphine derivatives of the methanobenzazocine family that act as potent analgesics.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of SKELETAL MYOCYTES. Defects in the SCN4A gene, which codes for the alpha subunit of this sodium channel, are associated with several MYOTONIC DISORDERS.
A 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.
Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.
A 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.
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)
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
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.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning.
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.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The ability of a substrate to allow the passage of ELECTRONS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Batrachotoxin is the 20-alpha-bromobenzoate of batrachotoxin A; they are toxins from the venom of a small Colombian frog, Phyllobates aurotaenia, cause release of acetylcholine, destruction of synaptic vesicles and depolarization of nerve and muscle fibers.
A voltage-gated sodium channel subtype found in neuronal tissue that mediates the sodium ion PERMEABILITY of excitable membranes.
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.
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.
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.
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.
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).
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.
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.
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.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.
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.
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
The rate dynamics in chemical or physical systems.
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.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
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.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
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.
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.
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 that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
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.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.
A calcium channel blocker that is a class IV anti-arrhythmia agent.
A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The 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.
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.
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.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
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.
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.
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.
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.
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.
Regularly spaced gaps in the myelin sheaths of peripheral axons. Ranvier's nodes allow saltatory conduction, that is, jumping of impulses from node to node, which is faster and more energetically favorable than continuous conduction.
A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
A 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.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
Use of electric potential or currents to elicit biological responses.
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
Elements of limited time intervals, contributing to particular results or situations.
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.
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)
Benzoic acid or benzoic acid esters substituted with one or more nitro groups.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
Insects of the order Dictyoptera comprising several families including Blaberidae, BLATTELLIDAE, Blattidae (containing the American cockroach PERIPLANETA americana), Cryptocercidae, and Polyphagidae.
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.
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.
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.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.
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.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
A 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.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
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.
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.
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.
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.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium 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.
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.
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.
A ubiquitous sodium salt that is commonly used to season food.
A voltage-gated sodium channel beta subunit that binds covalently to voltage-gated alpha subunits.
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.
Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
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.
Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION 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.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The hollow, muscular organ that maintains the circulation of the blood.
Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.
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.
Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.
A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
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.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A family of 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.
A voltage-gated potassium channel that is expressed primarily in the HEART.
A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.
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.
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.
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.
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.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
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.
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)
An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Agents that promote the excretion of urine through their effects on kidney function.
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.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
The physical characteristics and processes of biological systems.
An inhibitor of anion conductance including band 3-mediated anion transport.
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
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.
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
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.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
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)
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A 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.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
Proteins obtained from species in the class of AMPHIBIANS.
A genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel.
A 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.
Contractile tissue that produces movement in animals.
CALCIUM CHANNELS located in the neurons of the brain.
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A 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.
A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.
The 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.
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.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electrical charges.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.
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.
An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.
Polycyclic ethers produced by Gambierdiscus (DINOFLAGELLATES) from gambiertoxins, which are ingested by fish which in turn may be ingested by humans who are susceptible to the CIGUATERA POISONING.
A 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.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
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.

Biophysical characterization of M1476I, a sodium channel founder mutation associated with cold-induced myotonia in French Canadians. (1/29)

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Multicenter study of voriconazole pharmacokinetics and therapeutic drug monitoring. (2/29)

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Sodium current deficit and arrhythmogenesis in a murine model of plakophilin-2 haploinsufficiency. (3/29)

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The human Nav1.5 F1486 deletion associated with long QT syndrome leads to impaired sodium channel inactivation and reduced lidocaine sensitivity. (4/29)

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Tetrodotoxin-resistant voltage-dependent sodium channels in identified muscle afferent neurons. (5/29)

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Novel bioactivation mechanism of reactive metabolite formation from phenyl methyl-isoxazoles. (6/29)

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Central mechanisms of menthol-induced analgesia. (7/29)

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Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry. (8/29)

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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 ...
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
KEY POINTS: During exercise, blood pressure (BP) response is exaggerated in peripheral artery disease (PAD). We examined whether heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in PAD rats. With HT (increase in the Tm of â ¼1.5°C for 30 min, 2 times daily for 3 continuous days), the amplified BP response to muscle contraction is alleviated in PAD. We demonstrated that HT attenuates the enhancement of the BP response induced by stimulation of P2X in muscle afferent nerves of PAD rats. HT also attenuates the upregulation of the P2X3 and the increase in P2X currents in the muscle afferent neurons of PAD rats. Prior heat exposure plays a beneficial role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction in the activity of the P2X receptor pathway is likely a part of the mechanism mediating this improvement. ABSTRACT: The current study was performed to examine if heat treatment (HT) has beneficial effects on the exaggerated ...
AmbroxolHCl is a potent inhibitor of the neuronal Na+ channels, inhibits TTX-resistant Na+ currents with IC50 of 35.2 uM and 22.5 μM for tonic and phasic block, inhibits TTX-sensitive Na+ currents with IC50 of 100 μM. Phase 3.
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. Further investigations indicate that senescence does not contribute to MLN0128-mediated repression of xenograft MCC tumor growth. Finally we also observe robust antitumor effects of MLN0128 when administered as a dual therapy with JQ1 a bromodomain protein BRD4 inhibitor. These results suggest dual blockade of PI3K/mTOR pathway and c-Myc axis is effective in the control of MCC tumor growth. Our results demonstrate that MLN0128 is potent as monotherapy or as a member of combination therapy with JQ1 for advanced MCC. culture experiments with MCC cells followed by Western blot analysis. We first treated MCC cells with or without different concentrations of MLN0128 for 24 hours and then examined the total and phosphorylated protein profile of the targeted pathways by Western blotting. Consistent with published reports on other solid tumors MLN0128 markedly inhibited phosphorylation of both mTOR CI994 (Tacedinaline) and its ...
Voltage-gated Na+ channels (VGSCs) are heteromeric protein complexes containing pore-forming ? subunits together with non-pore-forming ? subunits. There are nine ? subunits, Nav1.1-Nav1.9, and four ? subunits, ?1-?4. The ? subunits are multifunctional, modulating channel activity, cell surface expression, and are members of the immunoglobulin superfamily of cell adhesion molecules. VGSCs are classically responsible for action potential initiation and conduction in electrically excitable cells, including neurons and muscle cells. In addition, through the ?1 subunit, VGSCs regulate neurite outgrowth and pathfinding in the developing central nervous system. Reciprocal signalling through Nav1.6 and ?1 collectively regulates Na+ current, electrical excitability and neurite outgrowth in cerebellar granule neurons. Thus, ? and ? subunits may have diverse interacting roles dependent on cell/tissue type. VGSCs are also expressed in non-excitable cells, including cells derived from a number of types of cancer. In
TY - JOUR. T1 - Neuronal voltage-gated sodium channel subtypes. T2 - Key roles in inflammatory and neuropathic pain. AU - Ekberg, J.. AU - Adams, David J.. PY - 2006. Y1 - 2006. N2 - Voltage-gated sodium channels (VGSCs) play an important role in neuronal excitability. Regulation of VGSC activity is a complex phenomenon that occurs at multiple levels in the cell, including transcriptional regulation, post-translational modification and membrane insertion and retrieval. Multiple VGSC subtypes exist that vary in their biophysical and pharmacological properties and tissue distribution. Any alteration of the VGSC subtype profile of a neuron or the mechanisms that regulate VGSC activity can cause significant changes in neuronal excitability. Inflammatory and neuropathic pain states are characterised by alterations in VGSC subtype composition and activity in sensory neurons. This review focuses on the VGSC subtypes involved in such pain states.. AB - Voltage-gated sodium channels (VGSCs) play an ...
Brevetoxin B (Brevetoxin-2; PbTx-2) is a polyketide neurotoxin produced by Karenia species and other dinoflagellates. Brevetoxin B binds to site 5 on the alpha subunit of voltage-gated sodium channels (IC50=15 nM) on neurons at the neuromuscular junction, causing the channel to open irreversibly at potentials more negative than normal, discharging action potentials repetitively. Brevetoxin B is ichthyotoxic at nanomolar concentrations and is responsible for an illness described as neurotoxic shellfish poisoning. - Mechanism of Action & Protocol.
Amiloride hydrochloride (MK-870 hydrochloride) is an inhibitor of both epithelial sodium channel (ENaC) and urokinase-type plasminogen activator receptor (uTPA). Amiloride hydrochloride is a blocker of polycystin-2 (PC2; TRPP2) channel. - Mechanism of Action & Protocol.
Kim DY, Carey BW, Wang H, Ingano LA, Binshtok AM, Wertz MH, Pettingell WH, He P, Lee VM, Woolf CJ, Kovacs DM. BACE1 regulates voltage-gated sodium channels and neuronal activity ...
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 ...
Triamterene blocks epithelial Na+ channel (ENaC) in a voltage-dependent manner with IC50 of 4.5 μM. Buy Sodium Channel inhibitor Triamterene from AbMole BioScience.
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Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Although β subunits were originally termed auxiliary, we now know that they are multifunctional …
... is a voltage-gated sodium channel (VGSC) blocker. It is a selective blocker of the inactivated state of VGSCs, ... preferentially inhibiting persistent sodium current. It has been proposed that cenobamate additionally enhances presynaptic ...
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". ...
... 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, ... Quinidine also blocks certain voltage-gated potassium channels (e.g., Kv1.4, Kv4.2, hERG, among others), acts as an ... Hugues Abriel (1 September 2015). Cardiac Sodium Channel Disorders, An Issue of Cardiac Electrophysiology Clinics, E-Book. ...
ZTX is an extremely potent sodium channel blocker. It has been shown to block the voltage-gated sodium channels at picomolar ... Voltage-gated sodium channel Saxitoxin Tetrodotoxin Yotsu-Yamashita, M.; Kim, Y. H.; Dudley, S. C.; Choudhary, G.; Pfahnl, A.; ... A potent sodium-channel blocker". Proceedings of the National Academy of Sciences. 101 (13): 4346-4351. Bibcode:2004PNAS.. ...
Tarnawa I, Bölcskei H, Kocsis P (January 2007). "Blockers of Voltage-Gated Sodium Channels for the Treatment of Central Nervous ... "Voltage-gated", also called "voltage-sensitive" and "voltage-dependent" sodium channel also known as "VGSCs" or "Nav channel" ... of some voltage gated sodium channels in a very powerful and reversible manner, without affection of other ion channels. " ... Site 1 binds the sodium channel blockers tetrodotoxin and saxitoxin. Site 2 binds lipid-soluble sodium channel activators such ...
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/ ...
... voltage-gated sodium channel blocker. One of the most potent known natural toxins, it acts on the voltage-gated sodium channels ... Opening of the voltage-gated sodium channel occurs when there is a change in voltage or some ligand binds in the right way. It ... The voltage-gated sodium channel is essential for normal neuronal functioning. It exists as integral membrane proteins ... "Protection against nerve toxicity by monoclonal antibodies to the sodium channel blocker tetrodotoxin". Journal of Clinical ...
... is a voltage-gated sodium channel blocker with anticonvulsant and mood-stabilizing effects that is related to ...
... as a non-selective voltage-gated sodium channel blocker.[citation needed] As of January 2018, it is in phase III clinical ... "Recent progress in sodium channel modulators for pain". Bioorganic & Medicinal Chemistry Letters. 24 (16): 3690-9. doi:10.1016/ ... Vixotrigine was originally claimed to be a selective central Nav1.3 blocker, but was subsequently redefined as a selective ... peripheral Nav1.7 blocker.[citation needed] Following this, vixotrigine was redefined once again, ...
All of the anticonvulsants routinely used to treat bipolar disorder are blockers of voltage-gated sodium channels, affecting ...
... 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 ... Nevitt SJ, Marson AG, Weston J, Tudur Smith C (August 2018). "Sodium valproate versus phenytoin monotherapy for epilepsy: an ...
It works as a non-selective voltage-gated sodium channel blocker and belongs to the Class IB group of anti-arrhythmic ... The LQT3 form of long QT syndrome is amenable to treatment with mexiletine as this form is caused by defective sodium channels ... is a class IB antiarrhythmic which prolongs the refractory period by delaying the recovery from inactivation of sodium channels ...
... is a selective, small-molecule Nav1.7 and Nav1.8 voltage-gated sodium channel blocker under development by Pfizer ... Bagal SK, Chapman ML, Marron BE, Prime R, Storer RI, Swain NA (August 2014). "Recent progress in sodium channel modulators for ... Martz L (June 2014). "Nav-i-gating antibodies for pain". SciBX: Science-Business EXchange. 7 (23): 662. doi:10.1038/scibx. ...
... act as a voltage-gated sodium channel blocker, and displays estrogenic activity in rodents. In contrast to ibogaine and other ...
... 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 ...
... is a drug which acts as a dual noncompetitive antagonist of the AMPA receptor and neuronal voltage-gated sodium channel blocker ...
... is a selective small-molecule Nav1.7 and Nav1.8 voltage-gated sodium channel blocker which is under development by ... Bagal SK, Chapman ML, Marron BE, Prime R, Storer RI, Swain NA (August 2014). "Recent progress in sodium channel modulators for ... List of investigational analgesics Martz L (2014). "Nav-i-gating antibodies for pain". Science-Business EXchange. 7 (23): 662. ...
Chilean tarantula venom that acts as both a voltage-gated calcium channel blocker and a voltage-gated sodium channel blocker. ... GTx1-15 targets low-voltage activated cation channels. It specifically inhibits: T-type calcium channel Cav3.1 Sodium channels ... sodium channels (Nav1.7 and Nav1.3), but has a minimal effect on tetrodotoxin-resistant sodium channels (Nav1.5 and Nav1.8). ... It is homologous in sequence with sodium channel blocker PaurTx3 by 76.5%, and it also shares similarities in sequence with ...
Sodium channels were the first voltage-gated ion channels to be isolated in 1984 from the eel Electrophorus electricus by ... The pufferfish toxin tetrodotoxin (TTX), a sodium channel blocker, was used to isolate the sodium channel protein by binding it ... As with sodium channels, the potassium channels have their own toxins that block channel protein action. An example of such a ... Cloning the channel itself allowed for applications such as identifying the same channels in other animals. Sodium channels are ...
... is also a potent blocker of voltage-gated sodium channels, and this action is thought to be involved in both its ... Bertelsen, Anne K.; Backonja, Misha-Miroslav (2007). "Drugs Targeting Voltage-Gated Sodium and Calcium Channels". Encyclopedia ... August 2007). "Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin". Biochemical Pharmacology. 74 ...
... as well as a blocker of voltage-gated sodium channels (VGSCs). The antidepressant effects of dosulepin are thought to be due to ... and sodium channel-blocking effects. Dosulepin is used for the treatment of major depressive disorder. There is clear evidence ... Dosulepin is a transporter blocker of the serotonin transporter (SERT) and the norepinephrine transporter (NET), thereby acting ... low blood sodium) Movement disorders Dyspepsia (indigestion) Increased intraocular pressure Changes in blood sugar levels ...
... nicotinic acetylcholine receptor blockers (15), ecdysone receptor agonists (18), volgate-gated sodium channel blockers (22A and ... voltage-gated sodium channel modulators (3A), nicotinic acetylcholine receptor modulators (5), chloride channel activators (6 ... but is not yet reported for another voltage-dependent sodium channel blocker, metafumizone (22B). (These two mutations, as with ... a nicotinic acetylcholine receptor channel blocker (IRAC group 14), began to show low to moderate efficacy decline in South ...
... is a non-selective blocker of multiple ion channels, in particular, voltage-gated sodium channels Nav1.3, Nav1.5 ... and Nav1.8 neuronal voltage-gated sodium channels more potently than Nav1.2 and Nav1.6 channels expressed in Xenopus oocytes". ... voltage-gated potassium channels Kv7.2/ Kv7.3, Kv7.1, Kv7.1/KCNE1, and hERG. Inhibition of serotonin and norepinephrine ... Nau C, Seaver M, Wang SY, Wang GK (March 2000). "Block of human heart hH1 sodium channels by amitriptyline". J Pharmacol Exp ...
... and Nav1.8 voltage-gated sodium channel blocker ADE-615 - undefined mechanism of action ADE-616 - undefined mechanism of action ... CS1 maint: discouraged parameter (link) "Sodium benzoate - SyneuRx - AdisInsight". adisinsight.springer.com. Springer. ... phosphodiesterase 10A inhibitor Sodium benzoate (SND-11, SND-12, SND-13, SND-14; Clozaben, NaBen) - D-amino acid oxidase ... inhibitor TAK-831 - D-amino acid oxidase inhibitor AUT-00206 - shaw potassium channel modulator Evenamide (NW-3509; NW-3509A ...
... atypical voltage-gated sodium channel blocker [9] DSP-2230 - selective Nav1.7 and Nav1.8 blocker [10] Funapide (TV-45070, ... selective Nav1.7 blocker [13] NKTR-171 - voltage-gated sodium channel blocker [14] PF-05089771 - selective Nav1.7 and Nav1.8 ... non-selective voltage-gated sodium channel blocker [18][citation needed] VX-150 - selective Nav1.8 blocker [19] HSK16149 - ... blocker [15] Ralfinamide (NW-1029) - non-selective voltage-gated sodium channel blocker, as well as other actions [16] ...
... tetrodotoxin-sensitive voltage-gated sodium channels (TTX-s Na+ channels) and tetrodotoxin-resistant voltage-gated sodium ... Tetrodotoxin is a sodium channel blocker. It inhibits the firing of action potentials in neurons by binding to the voltage- ... Tetrodotoxin binds to what is known as site 1 of the fast voltage-gated sodium channel. Site 1 is located at the extracellular ... The use of this toxin as a biochemical probe has elucidated two distinct types of voltage-gated sodium channels present in ...
... block the voltage gated sodium channels Calcium channel blockers - in general have negative bathmotropic effects ... electrochemical changes begin to take place in the voltage-gated rapid sodium channels, which permit the rapid influx of sodium ... When enough sodium channels are opened, so that the rapid influx of sodium ions is greater than the tonic efflux of potassium ... Likewise, when the sodium channels are in a state of greater activation, then the influx of sodium ions that allows the ...
... channel, a type of voltage-gated potassium channel, and as a blocker of voltage-gated sodium channels, including Nav1.2 and ... of the hERG channels at maximum affinity suggests that APETx1 is a gating modifier. APETx1 blocks voltage-gated sodium channels ... In addition, APETx1 blocks several mammalian voltage-gated sodium channels, including Nav1.2 with an IC50 of 31 nM, and Nav1.8 ... APETx1 inhibits the hERG channel, a type of voltage-gated potassium channel. APETx1 is thought to interact with three aromatic ...
Ciguatoxin lowers the threshold for opening voltage-gated sodium channels in synapses of the nervous system. Opening a sodium ... There is some evidence that calcium channel blockers like nifedipine and verapamil are effective in treating some of the ... channel causes depolarization, which could sequentially cause paralysis, heart contraction, and changing the senses of hot and ...
Medications that influence voltage-gated sodium ion channels are under investigation as a potential neuroprotective strategy ... Yang C, Hao Z, Zhang L, Zeng L, Wen J (October 2015). "Sodium channel blockers for neuroprotection in multiple sclerosis". The ... Currently, there is insufficient evidence of an effect of sodium channel blockers for people with MS. MS is a clinically ... Antibiodies against the Kir4.1 potassium channel may be related to MS. In 2008, vascular surgeon Paolo Zamboni suggested that ...
voltage-gated ion channel activity. • ion channel activity. • protein binding. • alpha-actinin binding. • voltage-gated calcium ... Zühlke RD, Bouron A, Soldatov NM, Reuter H (May 1998). "Ca2+ channel sensitivity towards the blocker isradipine is affected by ... high voltage-gated calcium channel activity. • voltage-gated calcium channel activity involved in AV node cell action potential ... L-type voltage-gated calcium channel complex. • integral component of plasma membrane. • cell junction. • dendrite. • ...
These studies suggested that lamotrigine acts presynaptically on voltage-gated sodium channels to decrease glutamate release. ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) ... It is a triazine derivate that inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membranes. It ... As is the case for antiepileptic drugs that act on voltage-dependent sodium channels, lamotrigine thereby inhibits the release ...
... the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D-adrenoceptor ADRA1D gene.[58] ... Sodium. VGSCs. Blockers. *Antianginals: Ranolazine. *Antiarrhythmics (class I): Ajmaline. *Aprindine. *Disopyramide. * ... The cause is thought to be blockade of hERG voltage-gated potassium channels.[41][42] The risks are dose-dependent, and appear ...
Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine) ... including suppression of voltage-gated Ca2+ currents and activation of G protein-coupled receptor-operated K+ currents). ... and sodium channels in the cardiac muscle, leading to decreased cardiac conduction and cardiotoxicity. Selectivity of ...
Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as funapide and ... Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and ... N-type calcium-channel blocker.. Intrathecal.. Protein binding = 50%; half-life = 2.9-6.5 hours; excretion = urine (,1%).[122] ... Comes in free acid and sodium salt form, sodium salt is the form used in human medicine; practically insoluble in water (free ...
Mg2+ blocks the NMDA receptor channel in a voltage-dependent manner. The channels are also highly permeable to Ca2+. Activation ... While the opening and closing of the ion channel is primarily gated by ligand binding, the current flow through the ion channel ... Uncompetitive NMDA receptor antagonists, or channel blockers, enter the channel of the NMDA receptor after it has been ... thus allowing a voltage-dependent flow of sodium (Na+) and calcium (Ca2+) ions into the cell and potassium (K+) out of the cell ...
This means that the principal ions gated by AMPARs are sodium and potassium, distinguishing AMPARs from NMDA receptors (the ... However, AMPAR endocytosis has also been activated by voltage-dependent calcium channels, agonism of AMPA receptors, and ... Putrescine; Uncompetitive pore blockers (mostly dizocilpine site): 2-MDP. *3-HO-PCP ... Ion channel function[edit]. Each AMPAR has four sites to which an agonist (such as glutamate) can bind, one for each subunit.[5 ...
... properties of diazepam and other benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels ... The GABAA receptors are ligand-gated chloride-selective ion channels that are activated by GABA, the major inhibitory ... Benzodiazepines act via micromolar benzodiazepine binding sites as calcium channel blockers and significantly inhibit ... Sustained repetitive firing seems limited by benzodiazepines' effect of slowing recovery of sodium channels from inactivation.[ ...
By gating mechanism. Ion channel class. *Ligand-gated. *Light-gated. *Voltage-gated ... ion channel activity. • protein binding. • actin binding. • calcium channel activity. • cation channel activity. • protein ... Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of ... cation channel complex. Biological process. • regulation of cytosolic calcium ion concentration. • positive regulation of ...
Bennett DL, Clark AJ, Huang J, Waxman SG, Dib-Hajj SD (April 2019). "The Role of Voltage-Gated Sodium Channels in Pain ... this disorder can be in the voltage-gated sodium channel SCN9A (Nav1.7).[6] Patients with such mutations are congenitally ... Nav1.7 channels are expressed at high levels in nociceptive neurons of the dorsal root ganglia. As these channels are likely ... Profile of Ashlyn Blocker, 13, who has congenital insensitivity to pain.. Retrieved from "https://en.wikipedia.org/w/index.php? ...
One type is generated by voltage-gated sodium channels, the other by voltage-gated calcium channels. Sodium-based action ... beta blockers, and verapamil.[aj] ... Voltage-gated sodium channels are responsible for the fast ... although raising Vm opens most gates in the voltage-sensitive sodium channel, it also closes the channel's "inactivation gate ... Key: a) Sodium (Na+) ion. b) Potassium (K+) ion. c) Sodium channel. d) Potassium channel. e) Sodium-potassium pump.. In the ...
Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as funapide and ... Ziconotide, a blocker of potent N‐type voltagegated calcium channels, is administered intrathecally for the relief of severe, ... Gabapentinoids work as α2δ-subunit blockers of voltage-gated calcium channels, and tend to have other mechanisms of action as ... Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and ...
IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs ... Sodium. VGSCs. Blockers. *Antianginals: Ranolazine. *Antiarrhythmics (class I): Ajmaline. *Aprindine. *Disopyramide. * ... at its operating voltage range. These channels are not perfect rectifiers, as they can pass some outward current in the voltage ... "Inward rectifier potassium channels in plants differ from their animal counterparts in response to voltage and channel ...
Voltage-gated sodium channel. Open channel (top) carries an influx of Na+ ions, giving rise to depolarization. As the channel ... Depolarization blockersEdit. There are drugs, called depolarization blocking agents, that cause prolonged depolarization by ... While the sodium-potassium pump continues to work, the voltage-gated sodium and calcium channels that had been closed while the ... such as ion channels, sodium potassium pumps, and voltage-gated ion channels. ...
... δ subunit-containing voltage-gated calcium channel blocker or gabapentinoid may be its true primary mechanism of action, and ... GHB (sodium oxybate) and analogues. *Glucocorticoids (corticosteroids) (e.g., dexamethasone, prednisone). *nACh receptor ... α2δ subunit-containing voltage-dependent calcium channels blockers (gabapentinoids) (e.g., gabapentin, pregabalin, phenibut) ... Subsequent research has found that it is also a potent blocker of α2δ subunit-containing voltage-dependent calcium channels ( ...
"Voltage-dependent blockade of diverse types of voltage-gated Ca2+ channels expressed in Xenopus oocytes by the Ca2+ channel ... Bepridil (trade name Vascor) is an amine calcium channel blocker once used to treat angina. It is no longer sold in the United ... Sodium. VGSCs. Blockers. *Antianginals: Ranolazine. *Antiarrhythmics (class I): Ajmaline. *Aprindine. *Disopyramide. * ...
... in particular the so-called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, ... portion of the sodium channel. Local anesthetic drugs bind more readily to sodium channels in an activated state, thus onset of ... LA drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, ...
W. A. Catterall: From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. In: ... Auch Riluzol ist ein Natriumkanal-Blocker und wirkt neuroprotektiv. LiteraturBearbeiten. *T. M. Jessell, E. R. Kandel, J. H. ... F. H. Yu, W. A. Catterall: Overview of the voltage-gated sodium channel family. In: Genome Biol. 4 (3), 2003, S. 207. doi: ... Nomenclature and structure-function relationships of voltage-gated sodium channels. In: Pharmacol Rev. 57 (4), 2005, S. 397-409 ...
Uncompetitive antagonist (e.g. channel blocker) picrotoxin[citation needed], cicutoxin Negative allosteric modulators ... GABAA in which the receptor is part of a ligand-gated ion channel complex[5] ... makes the voltage across the cell's membrane less negative), shunting (has no effect on the cell's membrane potential), or ... GABAB metabotropic receptors, which are G protein-coupled receptors that open or close ion channels via intermediaries (G ...
Voltage-gatedEdit. Main article: voltage-gated calcium channel. Type. Voltage. α1 subunit (gene name). Associated subunits. ... L-type calcium channel blockers are used to treat hypertension. In most areas of the body, depolarization is mediated by sodium ... It is sometimes synonymous as voltage-gated calcium channel,[1] although there are also ligand-gated calcium channels.[2] ... "Voltage-Gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
... delta subunits of voltage-gated calcium channels". Trends in Pharmacological Sciences. 28 (5): 220-8. doi:10.1016/j.tips. ... and acts as a calcium channel blocker.[11][10][12]. Gabapentin was first approved for use in 1993.[13][14] It has been ... and the sodium-dependent multivitamin transporter (SMVT), and no saturation of bioavailability has been observed with the drug ... Gabapentin is a gabapentinoid, or a ligand of the auxiliary α2δ subunit site of certain voltage-dependent calcium channels ( ...
... which in turn leads to opening of voltage gated calcium channels and neurotransmitter release. This begins the process of ... Two common potassium channel blockers are Doxapram and GAL-021. Both act on potassium channels in Carotid Bodies. These cells ... Ligand binding causes AMPA receptors to open and allow for sodium ions to flow into the cell, leading to depolarization and ... Doxapram blocks leak potassium channels in the Tandom pore domain family of potassium channels while GAL-021 blocks BK channels ...
Zakon, H. H. (2012). "Adaptive evolution of voltage-gated sodium channels: The first 800 million years". Proceedings of the ... the R-type channel (R stands for Resistant to the other blockers and toxins, except SNX-482) involved in poorly defined ... Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ... High-voltage-gated calcium channels include the neural N-type channel blocked by ω-conotoxinGVIA, ...
"Voltage-gated calcium channels in the human adrenal and primary aldosteronism". J Steroid Biochem Mol Biol. 144 (part B): 410- ... which suggests that calcium-channel blockers may directly influence the adrenocortical biosynthesis of aldosterone in vivo.[9] ... primarily sodium and potassium, by acting on the distal convoluted tubule of kidney nephrons to: increase sodium reabsorption, ... with recorded membrane voltages that are too hyperpolarized to permit Ca2+ channels entry.[2] However, mouse zona glomerulosa ...
Selective blockers of Nav1.7 and Nav1.8 voltage-gated sodium channels, such as CNV1014802 and Funapide, are being investigated ... 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 ... Wood JN, Boorman J (2005). "Voltage-gated sodium channel blockers; target validation and therapeutic potential". Curr Top Med ...
Ziconotide is a voltage-gated calcium channel blocker which may be used in severe cases of ongoing neuropathic pain[47] it is ... Carbamazepine is a voltage-gated sodium channel inhibitor, and reduces neuronal excitability by preventing depolarisation.[26] ... There may be an increase in the expression or activity of voltage gated sodium and calcium channels which will support action ... Ion channel blockers. *Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, ...
"Adaptive evolution of voltage-gated sodium channels: the first 800 million years" (PDF). Proceedings of the National Academy of ... the R-type channel (R stands for Resistant to the other blockers and toxins, except SNX-482) involved in poorly defined ... Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ... "Voltage-Gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
Benzodiazepines acted via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit ... "Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations" (PDF) ... Riss, J.; Cloyd, J.; Gates, J.; Collins, S. (Aug 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics" (PDF) ... Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium ...
This depolarization opens some voltage-gated sodium channels, but also increases the inactivation at the same time. Since ... Therefore, beta blockers can cause the rise in potassium levels due to blockage of beta-2 receptors. However, the rise ... SCN4A is an important component of sodium channels in skeletal muscles. During exercise, sodium channels would open to allow ... But in hyperkalemic periodic paralysis, sodium channels are slow to close after exercise, causing excessive influx of sodium ...
Voltage-Gated Sodium Channel Blockers; Target Validation and Therapeutic Potential. Author(s): John N. Wood, James Boorman. ... John N. Wood and James Boorman, " Voltage-Gated Sodium Channel Blockers; Target Validation and Therapeutic Potential", Current ... Voltage-gated sodium channels are encoded by a family of ten structurally-related genes that are expressed in spatially and ... Abstract: Voltage-gated sodium channels are encoded by a family of ten structurally-related genes that are expressed in ...
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 ... Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the ...
Voltage-Gated Sodium Channel Blockers Library from OTAVA. . Biblioteca virtual para leer y descargar libros, documentos, ... Keywords : voltage-gated sodium channels membrane proteins inhibitors voltage-gated sodium channel blockers ligand-based ... Voltage-Gated Sodium Channel Blockers Library from OTAVA - Descarga este documento en PDF. Documentación en PDF para descargar ... offers new Voltage-gated sodium channel blockers library containing 1630 compounds. The library was designed as a special ...
Tetrodotoxin (TTX) is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered in these fish and found in several other aquatic animals (e.g., in blue-ringed octopuses, rough-skinned newts, and moon snails), it is actually produced by certain infecting or symbiotic bacteria like Pseudoalteromonas, Pseudomonas, and Vibrio as well as other species found in the animals ...
Selective blockers of Nav1.7 and Nav1.8 voltage-gated sodium channels, such as CNV1014802 and Funapide, are being investigated ... 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 ... Wood JN, Boorman J (2005). "Voltage-gated sodium channel blockers; target validation and therapeutic potential". Curr Top Med ...
... electrophysiology and gene targetting and behavioural approaches to explore the channels, receptors transcription factors and ... Wood JN, Boorman J (2005). Voltage-gated sodium channel blockers; target validation and therapeutic potential.. Curr Top Med ... Malik-Hall M, Wood JN, Okuse K (2003). Voltage-gated sodium channels. In Moss SJ, Henley J (Ed.), Receptor and Ion Channel ... Malik-Hall M, Wood J, Okuse K, Henley J (2002). Voltage-gated Sodium channels in Receptor and Ion Channel Traficking. In (Ed ...
Voltage-Gated Sodium Channel Blockers. Sodium Channel Blockers. Membrane Transport Modulators. Molecular Mechanisms of ...
Voltage-Gated Sodium Channel Blockers. Sodium Channel Blockers. Membrane Transport Modulators. Molecular Mechanisms of ...
Voltage-Gated Sodium Channel Blockers. To Top. *For Patients and Families. *For Researchers ...
Voltage-Gated Sodium Channel Blockers. Sodium Channel Blockers. Membrane Transport Modulators. Molecular Mechanisms of ...
... a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp ... The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of ... voltage-gated sodium channel blockers neuropathic pain; α-aminoamide derivatives; voltage-gated sodium channel blockers ... The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of ...
voltage-gated sodium channel blocker Any sodium channel blocker that interferes with the activity of voltage-gated sodium ... indoxacarb (CHEBI:38630) has role voltage-gated sodium channel blocker (CHEBI:38634) indoxacarb (CHEBI:38630) is a methyl ester ...
... and reversible inhibitor of voltage-gated sodium ion channels (NaVs). Modified forms of this toxin bearing cysteine-reactive ... Sodium Channel Blockers / chemistry* * Sodium Channel Blockers / pharmacology* * Sodium Channels / metabolism Substances * ... Maleimide Conjugates of Saxitoxin as Covalent Inhibitors of Voltage-Gated Sodium Channels J Am Chem Soc. 2013 Jul 24;135(29): ... and reversible inhibitor of voltage-gated sodium ion channels (NaVs). Modified forms of this toxin bearing cysteine-reactive ...
Voltage-gated sodium channels (Na,sub,v,/sub,s), which are coupled to synaptic vesicle exocytosis, are inhibited by volatile ... Voltage-Gated Sodium Channel Blockers / pharmacology* Substances * Anesthetics, General * Neurotransmitter Agents * Voltage- ... Voltage-gated sodium channels (Navs), which are coupled to synaptic vesicle exocytosis, are inhibited by volatile anesthetics ... Differential Inhibition of Neuronal Sodium Channel Subtypes by the General Anesthetic Isoflurane J Pharmacol Exp Ther. 2019 May ...
To test whether propranolol is unique among β-adrenergic receptor blockers in having sodium channel blocking activity, we ... Propranolol blocks cardiac and neuronal voltage-gated sodium channels. Dao W. Wang1,2, Akshitkumar M. Mistry1, Kristopher M. ... Voltage-gated sodium channels are established pharmacological targets for local anesthetics and many other drugs with shared ... We found that the ability of propranolol to block voltage-gated sodium channels is not stereospecific, nor a class effect of β- ...
9:50 Voltage gated sodium channels… perennial target for new pain therapies - are we making any progress. ... 9:10 Personalized medicine for pain, clinical validation with Nav1.7 blockers. Simon Tate, Chief Scientific Officer, ... P2X-7 ATP-gated ion channels are present in both neurons and glial cell. • Previous efforts in the clinic have been ... 10:50 P2X-7 ATP-gated ion channels in chronic pain: more validation and more challenges. ...
Eslicarbazepine acetate is a voltage-gated sodium channel blocker. It selectively targets the slow inactivated state of the ... 3- Vilin YY; Ruben PC, Slow inactivation in voltage-gated sodium channels: molecular substrates and contributions to ... Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, ... sodium ion channel (which have been implicated in the pathogenesis of epilepsy), preventing its return to the active state, and ...
Sodium voltage-gated channel alpha subunit 5 (channel blocker). Mass. *234.173 u ...
Our goal was to study the effects of AMD on peak and late sodium currents (INa,P and INa,L) and determine whether these effects ... Our goal was to study the effects of AMD on peak and late sodium currents (INa,P and INa,L) and determine whether these effects ... Amiodarone is a sodium channel blocker. To determine whether there is a difference between AMD and DES in their ability to ... Effects of Amiodarone and N-desethylamiodarone on Cardiac Voltage-Gated Sodium Channels. Mohammad-Reza Ghovanloo, Mena ...
0 (Catecholamines); 0 (Oxazepines); 0 (Voltage-Gated Sodium Channel Blockers); 0 (eleclazine); K94FTS1806 (Flecainide). ... BACKGROUND: Calmodulin (CaM) is a key modulator of the channel gating function of the ryanodine receptor (RyR). OBJECTIVE: The ... OBJECTIVE: The effectiveness of the novel cardiac late sodium inhibitor eleclazine in suppressing catecholamine-induced VT in a ... Eleclazine, an inhibitor of the cardiac late sodium current, is superior to flecainide in suppressing catecholamine-induced ...
To test the effects of several types of voltage-gated sodium channel (VGSC) blocker on nNav1.5 mRNA and protein expression and ... Pharmacological studies of voltage-gated sodium channel expression in human breast cancer cells : control of metastatic cell ... Two classes of blocker were used: a) Local anaesthetics (lidocaine and procaine) and (b) blockers of persistent current (INaP ... ranolazine and riluzole). In addition, a specific VGSC blocker, tetrodotoxin (TTX), was incorporated as a control. At ...
Sodium channels (also known as "voltage-gated sodium channels") are integral membrane proteins that conduct sodium ions (Na+) ... Blockers. Extracellular. The following naturally produced substances block sodium channels by binding to and occluding the ... This region plugs the channel after prolonged activation, inactivating it. Gating. Voltage-gated sodium channels have three ... Voltage-gated sodium channels play an important role in action potentials. If enough channels open when there is a change in ...
Voltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain ... Designing a C84 fullerene as a specific voltage-gated sodium channel blocker ... Voltage gated sodium channels as drug discovery targets. Sharan K Bagal, Brian E Marron, Robert M Owen, R Ian Storer, Nigel A ... The Role of Voltage-Gated Sodium Channels in Pain Signaling. David L. Bennett, Alex J. Clark, Jianying Huang, Stephen G. Waxman ...
Cenobamate is a voltage-gated sodium channel (VGSC) blocker. It is a selective blocker of the inactivated state of VGSCs, ... preferentially inhibiting persistent sodium current. It has been proposed that cenobamate additionally enhances presynaptic ...
Aptiom (eslicarbazepine acetate) is a voltage-gated sodium channel blocker. The precise mechanism(s) by which eslicarbazepine ... Aptiom (eslicarbazepine acetate) is a voltage-gated sodium channel blocker. The precise mechanism(s) by which eslicarbazepine ...
Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet. 2005 Jul 30-Aug 5. 366( ... Calcium Channel Blockers. Class Summary. Migraine prophylaxis has been reported with various calcium channel blockers, ... The calcium channel blocker with the highest evidence of efficacy is flunarizine, which is not available in the United States. ... Beta-Blockers. Class Summary. Beta-blockers are effective in migraine prophylactic therapy, possibly by blocking vasodilators, ...
Lamotrigine: sodium channel blocker. Carbamazepine: inhibits NA uptake and modulates voltage gated sodium channels. Thus, ... Specific binding site is the α2δ subunit of voltage-dependent calcium channels.. Due to binding of VGCC, GBP inhibits glutamate ... They also facilitate opening of K+ channels (causing hyperpolarization) and inhibit opening of Ca2+ channels (inhibiting ...
We examined how auxiliary β2 and β3 subunits and the phosphorylation state of the channel influence its biophysical... ... The voltage-gated sodium ion channel NaV1.7 is crucial in pain signaling. ... Furthermore, the β3 subunit reduced the susceptibility of NaV1.7α to several sodium channel blockers. In addition, we assessed ... an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. ...
Voltage-gated sodium channels. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance ... Holding voltage (mV). Reference. saxitoxin Rn. Pore blocker. 7.4. pKd. - -80.0 8,61. ... sodium channel, voltage-gated, type V, alpha subunit , sodium channel, voltage gated, type V alpha subunit , sodium channel ... 2012) A voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells. Nat. Immunol., 13 (9): 880-7. [ ...
  • 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. (wikidoc.org)
  • Sodium channels normally consist of an alpha subunit which forms the ion conduction pore and one to two beta subunits which have several functions including modulation of channel gating. (wikidoc.org)
  • [2] Expression of the alpha subunit alone is sufficient to produce a functional channel. (wikidoc.org)
  • An alpha subunit, consisting on its own of four repeating trans-membrane domains forming the actual pore, forms the core of the channel and is functional on its own. (axonmedchem.com)
  • SCN2A is a gene that codes for the alpha subunit of voltage-gated, type II sodium channels, and is highly expressed in the brain. (biomedcentral.com)
  • 3 ] reported de novo SCN2A mutations (which codes for the alpha subunit of voltage-gated, type II sodium channel) in three cases with ASD, one of which [ 3 ] will be described in detail herein. (biomedcentral.com)
  • Abstract : Voltage-gated sodium channels are a class of large integral membrane proteins, composed of a highly processed α subunit and one or several smaller β subunits. (duhnnae.com)
  • We examined how auxiliary β2 and β3 subunits and the phosphorylation state of the channel influence its biophysical properties and pharmacology. (springer.com)
  • This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied. (springer.com)
  • Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief. (ucl.ac.uk)
  • a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. (mdpi.com)
  • NaV1.7 flox'-Transgenic mouse expressing floxed NaV1.7 sodium channel gene (as described in Nassar et al. (uclb.com)
  • The four sodium channel subtypes that are of particular interest because of their restricted distribution in nociceptors are the tetrodotoxin-sensitive (TTX-S) channels NaV1.3 and NaV1.7 and the tetrodotoxin-resistant (TTX-R) channels NaV1.8 and NaV1.9. (uclb.com)
  • These channels are currently regarded as being amongst the best validated targets for pain therapy and in particular have caught widespread attention following the discovery of the remarkable analgesic phenotype associated with the loss-of-function NaV1.7 mutations in humans. (uclb.com)
  • Voltage-gated sodium channel Nav1.7 represents a promising target for pain relief. (proteopedia.org)
  • Here we report the cryo-EM structures of the human Nav1.7-beta1-beta2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with Protoxin-II and saxitoxin with Huwentoxin-IV, both determined at overall resolutions of 3.2 A. The two structures are nearly identical except for minor shifts of VSDII, whose S3-S4 linker accommodates the two GMTs in a similar manner. (proteopedia.org)
  • Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. (proteopedia.org)
  • GsAF-Ipeptide toxin is reported to block the following voltage-gated sodium channel isoforms: Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.6 and Nav1.7 with respective IC50 values of 0.4, 0.6, 1.3, 0.3, 1.2 and 0.04 µM. (creativebiomart.net)
  • The library was designed as a special screening collection comprising compounds with predicted sodium channels blocking activity and selectivity. (duhnnae.com)
  • G - glycosylation , P - phosphorylation , S - ion selectivity, I - inactivation, positive (+) charges in S4 are important for transmembrane voltage sensing. (wikidoc.org)
  • The pore of sodium channels contains a selectivity filter made of negatively charged amino acid residues, which attract the positive Na + ion and keep out negatively charged ions such as chloride . (wikidoc.org)
  • The functional characterization of GIIIC defines it as a canonical µ-conotoxin that displays substantial selectivity towards skeletal muscle sodium channels (Na V ), albeit with ~2.5-fold lower potency than GIIIA. (edu.au)
  • GIIIC exhibited a lower potency of inhibition of Na V 1.4 channels, but the same Na V selectivity profile when compared to GIIIA. (edu.au)
  • Counter to the prevailing view that olfactory PNs sum their inputs passively, we show for the first time that NMDA spikes within individual dendrites can both amplify OB inputs and impose combination selectivity upon them, while their ability to compartmentalize voltage signals allows different dendrites to represent different odorant combinations. (elifesciences.org)
  • Sodium selectivity of acid-sensing ion channels is mediated by negatively charged side chains and not by a size-exclusion mechanism. (elifesciences.org)
  • Efflux of xenobiotic fluoride from microorganisms occurs through a novel family of ion channels with stringent selectivity for fluoride ion and dual-topology molecular architecture. (elifesciences.org)
  • Because of the conflicting reports and the lack of a quantitative description of ketamine blockade, we investigated the local anesthetic-like action of ketamine in recombinantly expressed rat skeletal muscle (rSkM 1 ) voltage-gated sodium channels. (asahq.org)
  • The α-subunit and the accessory β 1 subunit of the rat skeletal muscle μ 1 sodium channel were inserted in a modified pBluescript (KS−) at the EcoR I site. (asahq.org)
  • Gating pore currents through the voltage-sensing domains (VSDs) of the skeletal muscle voltage-gated sodium channel NaV1.4 underlie hypokalemic periodic paralysis (HypoPP) type 2. (ugent.be)
  • LA drugs block the Na + channel pore, accessing their binding site in nerve and skeletal muscle mainly or entirely from the cytoplasm through the inner pore ( Narahashi and Frazier, 1971 ). (aspetjournals.org)
  • Therefore, the inhibition of voltage-gated sodium channels could be an effective strategy to prevent the development of these diseases. (duhnnae.com)
  • Sodium channel blockers are drugs which impair the conduction of sodium ions (Na + ) through sodium channels . (wikipedia.org)
  • Sodium channels (also known as "voltage-gated sodium channels") are integral membrane proteins that conduct sodium ions ( Na + ) through a cell's plasma membrane . (wikidoc.org)
  • Many of the ionotropic receptors are also able to conduct sodium ions. (wikidoc.org)
  • When stimulated by a change in transmembrane voltage , this region moves toward the extracellular side of the cell membrane, allowing the channel to become permeable to ions. (wikidoc.org)
  • Each of these variables can attain a value between 1 (fully permeant to ions) and 0 (fully non-permeant), the product of these variables yielding the percentage of conducting channels. (wikidoc.org)
  • Activation causes a conformational change of the receptor, leading to the opening of the internal pore, and enabling extra-cellular sodium ions to flow into the cell. (axonmedchem.com)
  • Action potential propagation along an axon is electrical, caused by the exchanges of sodium and potassium ions across the axonal membrane. (merckmanuals.com)
  • The force of diffusion then causes potassium ions to move down their concentration gradient, through the open potassium channels, and out of the cell. (jove.com)
  • Cell membranes are selectively permeable because most ions and molecules cannot cross the lipid bilayer without help, often from ion channel proteins that span the membrane. (jove.com)
  • The most common intra- and extracellular ions found in the nervous tissue are potassium (K + ), sodium (Na + ), chloride (Cl - ), and calcium (Ca 2+ ). (jove.com)
  • Differences in ion concentration between the inside and outside of neurons are primarily due to the activity of the sodium-potassium (Na + / K + ) pump-a transmembrane protein that continuously pumps three Na + ions out of the cell for every two K + ions it pumps in. (jove.com)
  • ENaCs are heterotrimeric proteins that form channels in the cell membrane and allow the passage of sodium ions (Na+). (phys.org)
  • Turning off the light or irradiating the cells with green light alters the shape of the compound in such a way that the block is released and sodium ions flow through the channel pore into the cell. (phys.org)
  • There has been much speculation that aberrant influx of sodium ions through ENaCs might contribute to the pathogenesis of neuronal diseases by causing persistent, uncontrolled firing by nerve cells. (phys.org)
  • In addition, our photoamiloride/ENaC system can be used to manipulate the polarization state of cells - the magnitude of the electrical potential across the cell membrane - by altering the flow of sodium ions through these channels," Dirk Trauner adds. (phys.org)
  • Ion channel proteins open and close ion permeation pathways in response to changes in membrane voltage, neurotransmitters and other chemical ligands, temperature and mechanical forces, enabling ions to move between cellular compartments to generate electrical and chemical signals that are fundamental for a diverse array of physiological cellular process. (elifesciences.org)
  • Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:7720699, PubMed:17167479, PubMed:25240195, PubMed:26680203, PubMed:15385606, PubMed:16988069, PubMed:17145499, PubMed:19369487, PubMed:24311784). (proteopedia.org)
  • Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions ( Na + ) through a cell's plasma membrane . (bionity.com)
  • They may be classified according to the trigger that opens the channel the such ions, i.e. either a voltage-change (voltage-gated sodium channels) or binding of a substance (a ligand) to the channel (ligand-gated sodium channels). (bionity.com)
  • Isoflurane at clinically relevant concentrations induced a hyperpolarizing shift in the voltage dependence of steady-state inactivation and slowed recovery from fast inactivation in all three Na v subtypes, with the voltage of half-maximal steady-state inactivation significantly more positive for Na v 1.1 (-49.7 ± 3.9 mV) than for Na v 1.2 (-57.5 ± 1.2 mV) or Na v 1.6 (-58.0 ± 3.8 mV). (nih.gov)
  • Genetic diseases that alter Na + channel inactivation cause muscle stiffness because of the introduction of a window current . (wikidoc.org)
  • Inhibition of kinase activity increased channel inactivation, while the blocking phosphatases produced the opposite effect. (springer.com)
  • Fast inactivation (τ = 1 ms for peak sodium current). (guidetopharmacology.org)
  • Description: IC50s were generated on a PatchXpress automated voltage-clamp platform, with the membrane potential maintained at a voltage yielding full inactivation of the channel. (guidetopharmacology.org)
  • Metaflumizone selectively inhibited Na v 1.4 channels at potentials that promoted slow inactivation and shifted the voltage dependence of slow inactivation in the direction of hyperpolarization. (aspetjournals.org)
  • Moreover, SCI insecticides typically cause hyperpolarizing shifts in the voltage dependence of slow inactivation and impede recovery from slow inactivation. (aspetjournals.org)
  • Benoit 3 reported no effect of ketamine on the sodium channel steady-state inactivation curve, but other investigators 1,10 found a shift in the hyperpolarized direction, a characteristic of local anesthetics. (asahq.org)
  • Cryo-EM structures of the gating cycle of bestrophin reveal the molecular underpinnings of activation and inactivation gating in this calcium-activated chloride channel and reveal a surprisingly wide pore. (elifesciences.org)
  • In excitable cells such as neurons and myocytes , sodium channels are responsible for the rising phase of action potentials . (wikidoc.org)
  • Berta T, Poirot O, Pertin M, Ji RR, Kellenberger S, Decosterd I (2008) Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain. (springer.com)
  • Akopian AN, Sivilotti L, Wood JN (1996) A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. (springer.com)
  • Black JA, Liu S, Tanaka M, Cummins TR, Waxman SG (2004) Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. (springer.com)
  • ion channels directly connect the cytoplasm of the presynaptic and postsynaptic neurons. (merckmanuals.com)
  • Pyramidal neurons in the piriform cortex are the main integration units within which the discrete molecular information channels of the OB are combined to form 'odor objects', but the biophysical and circuit-level mechanisms that remap LOT inputs into the olfactory code in PCx remain poorly understood. (elifesciences.org)
  • Experimentally, ketamine blocks sodium-dependent action potentials in dorsal root ganglion neurons, 1 cardiac myocytes, 2 and frog myelinated nerve fibers. (asahq.org)
  • Tetrodotoxin (TTX) is a small molecule that blocks voltage-gated sodium channels on neurons. (hindawi.com)
  • The voltage-gated sodium-channel type IX α subunit, known as Na v 1.7 and encoded by the gene SCN9A , is located in peripheral neurons and plays an important role in action potential production in these cells. (jci.org)
  • It is now clear that some sodium channel subtypes are selectively expressed in specialised damage-sensing peripheral neurons (nociceptors). (uclb.com)
  • However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. (biomedcentral.com)
  • The large-conductance calcium-activated potassium channels (BK Ca ) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. (biomedcentral.com)
  • The present study aimed to determine the effects of resveratrol on BK Ca currents and voltage-gated sodium currents in cortical neurons. (biomedcentral.com)
  • As BK Ca channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol. (biomedcentral.com)
  • Voltage-gated sodium channels in cardiomyocytes [ 47 ] and rat dorsal root ganglion neurons [ 21 ] are also blocked by resveratrol. (biomedcentral.com)
  • Despite this, the effects of resveratrol on the membrane properties and the ion channels of neurons have not yet been fully determined. (biomedcentral.com)
  • Therefore, the present study examined the effects of resveratrol on BK Ca currents and voltage-gated sodium currents by a voltage clamp setup in cortical neurons. (biomedcentral.com)
  • Disclosed are compounds of Formula A, or a salt thereof: Formula (A), wherein: Het, Q and R1A to R4A are defined herein, which compounds have properties for blocking Nav 1.7 ion channels found in peripheral and sympathetic neurons. (sumobrain.com)
  • Saxitoxin, a naturally occurring guanidinium poison, functions as a potent, selective, and reversible inhibitor of voltage-gated sodium ion channels (NaVs). (nih.gov)
  • Sodium channel inhibitor (SCI) insecticides selectively target voltage-gated sodium (Na v ) channels in the slow-inactivated state by binding at or near the local anesthetic receptor within the sodium channel pore. (aspetjournals.org)
  • Sodium channel inhibitor (SCI) drugs, an important group of therapeutic agents that include local anesthetics, class I anticonvulsants, and class I antiarrhythmics, have been in clinical use for more than a century. (aspetjournals.org)
  • 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)
  • The α-subunit forms ion-conducting aqueous pore whereas auxiliary β subunits modify the kinetics and voltage-dependence of channel gating. (duhnnae.com)
  • Diagram of a voltage-sensitive sodium channel α-subunit. (wikidoc.org)
  • An α subunit forms the core of the channel. (wikidoc.org)
  • When the α subunit protein is expressed by a cell, it is able to form channels which conduct Na + in a voltage-gated way, even if β subunits are not expressed. (wikidoc.org)
  • Furthermore, the β3 subunit reduced the susceptibility of Na V 1.7α to several sodium channel blockers. (springer.com)
  • The β3 subunit significantly influences the function of Na V 1.7α and, together with the phosphorylation of the channel, regulates its biophysical and pharmacological properties. (springer.com)
  • A large α-subunit, composed of approximately 2000 amino acids, forms the channel's pore and gating machinery and contains the principal drug binding sites. (aspetjournals.org)
  • Cannabidiol has been shown to cause inhibitory effects on sodium currents. (wikipedia.org)
  • The current literature suggests that cannabidiol inhibits sodium currents primarily through altering the biophysical properties of cell membrane, promoting the inactivated conformation of * sodium channels . (wikipedia.org)
  • Our goal was to study the effects of AMD on peak and late sodium currents (I Na,P and I Na,L ) and determine whether these effects change as AMD is metabolized into N -desethylamiodarone (DES). (frontiersin.org)
  • We tested the hypothesis that these toxins could function as blockers of the pathogenic gating pore currents. (ugent.be)
  • We report that a crab spider toxin Hm-3 from Heriaeus melloteei can inhibit gating pore currents due to mutations affecting the second arginine residue in the S4 helix of VSD-I that we have found in patients with HypoPP and describe here. (ugent.be)
  • Resveratrol concentration-dependently increased the current amplitude and the opening activity of BK Ca channels, but suppressed the amplitude of voltage-gated sodium currents. (biomedcentral.com)
  • Our data demonstrated that resveratrol activated BK Ca channels, but inhibited voltage-gated sodium currents. (biomedcentral.com)
  • Class I agents are grouped by their effect on the Na + channel, and by their effect on cardiac action potentials . (wikipedia.org)
  • The fast upstroke of action potentials is mediated by voltage-gated sodium channels, of which nine pore-forming α-subunits (Nav1.1-1.9) have been identified. (springer.com)
  • Because the influx of sodium is necessary to facilitate neuronal action potentials and signal conduction across sensory receptor membranes, the influx inhibition subsequently prevents the body reactions that would normally result from the neuronal signals 2 . (drugbank.ca)
  • An in vitro model of WM compression injury also found recovery of compound action potentials was enhanced when Ca 2+ was removed from the bathing medium or when the Na + channel blocker TTX was added in the presence of Ca 2+ ( Agrawal and Fehlings, 1996 ). (jneurosci.org)
  • Similar to the BK Ca channel opener NS1619, resveratrol decreased the firing rate of action potentials. (biomedcentral.com)
  • In particular, amylocaine, much like other local anesthetics, bind and blockade voltage gated sodium channels located in the excitable membranes of various sensory receptors 2 . (drugbank.ca)
  • From 2004 onwards, there has been extensive research on the use of adenosine, along with lignocaine/ procaine to induce depolarization arrest in the myocardium with minimal extracellular K + concentration which effectively inactivates the rapidly firing voltage gated Na + Channels along with use dependent sodium channel blockade achieved by the addition of the local anaesthetic. (pulsus.com)
  • Beta blockers have been consistent in reducing myocardial oxygen demand and providing myocardial protection in chronic heart failure, this property of beta blocker is effectively harnessed with addition of continuous esmolol infusion to Cardioplegia solution to produce diastolic arrest in addition to beta blockade induced heart rate reduction and reduction of myocardial resting oxygen demand with minimal extracellular K + concentration [ 8 ]. (pulsus.com)
  • The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. (mdpi.com)
  • Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity. (nih.gov)
  • 4 provide evidence for the safety and analgesic potential of neosaxitoxin, a site-1 sodium channel blocker. (asahq.org)
  • These channels may be the principal site of action of non-specific analgesic sodium channel blockers like lidocaine, and providing appealing targets for the development of selective blockers with fewer side effects. (uclb.com)
  • Our findings establish sodium channels as targets for propranolol and may help explain some beneficial effects of the drug in treating cardiac arrhythmias, and may explain certain adverse central nervous system effects. (frontiersin.org)
  • Voltage-gated sodium channels are established pharmacological targets for local anesthetics and many other drugs with shared mechanisms of action including certain anti-arrhythmic and anti-epilepsy agents. (frontiersin.org)
  • It selectively targets the slow inactivated state of the sodium ion channel (which have been implicated in the pathogenesis of epilepsy), preventing its return to the active state, and thereby reduces repetitive neuronal firing. (businesswire.com)
  • Voltage-gated sodium (Na + ) channels are targets for local anesthetic (LA) drugs that bind in the inner pore of the channel with affinities related to the channel gating states. (aspetjournals.org)
  • Sodium channels can often be isolated from cells as a complex of two types of protein subunits, α and β. (wikidoc.org)
  • When β subunits assemble with α subunits the resulting complex can display altered voltage dependence and cellular localization. (wikidoc.org)
  • Therefore, the β2 subunits did not change the biophysical properties of the channel. (springer.com)
  • In conclusion, co-expression of β subunits with Na V 1.7α, to better mimic the native channel properties, may be ineffective in cases when subunits are not associated, as shown in our experiments with β2. (springer.com)
  • Voltage-gated sodium channels (VGSCs) are composed of large pore-forming α subunits (Na v 1.1-Na v 1.9) and smaller auxiliary β subunits (β1-β4). (bmj.com)
  • However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). (mdpi.com)
  • Several other families of ion channels also have this architecture, including calcium-activated potassium (K Ca ) channels, cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels, and transient receptor potential (TRP) channels ( Fig. 1 and see below). (aspetjournals.org)
  • Cenobamate is a voltage-gated sodium channel (VGSC) blocker. (wikipedia.org)
  • Introduction Voltage-gated sodium channel (VGSC)-inhibiting drugs are commonly used to treat epilepsy and cardiac arrhythmia. (bmj.com)
  • In these studies, VGSC blockers altered prostate cancer cell morphology and arrested prostate cancer cell migration. (elsevier.com)
  • We have used rational drug design based on the phenytoin binding site in a VGSC to make novel sodium channel blockers with enhanced activity and minimal acute toxicity. (elsevier.com)
  • The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. (diva-portal.org)
  • Therefore we are very happy that we now have a pharmacological tool that acts primarily on this type of channel," Schönberger explains. (phys.org)
  • Black JA, Nikolajsen L, Kroner K, Jensen TS, Waxman SG (2008) Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas. (springer.com)
  • Neosaxitoxin and similar neurotoxins have low affinity for cardiac sodium channels (Na v 1.5) relative to their affinity for the sodium channel isoforms (Na v 1.7, Na v 1.8, and others) found in peripheral nerves. (asahq.org)
  • 5 The separation in neosaxitoxin affinities for sodium channel isoforms is at least an order of magnitude greater than that for any conventional local anesthetic. (asahq.org)
  • Voltage-gated sodium channels underlie electrical signalling in biological tissues and low doses of channel blockers have been used for many years as analgesics. (uclb.com)
  • Gating modifier toxins target ion channels by modifying the function of the VSDs. (ugent.be)
  • Gating modifier toxins may constitute useful hits for the treatment of HypoPP. (ugent.be)
  • OTAVA Ltd. offers new Voltage-gated sodium channel blockers library containing 1630 compounds. (duhnnae.com)
  • However, our results suggest that metaflumizone interacts with resting and fast-inactivated channels in a manner that is distinct from other compounds in this insecticide class. (aspetjournals.org)
  • These compounds bind the voltage-gated sodium channels responsible for producing peripheral nerve block with relatively low affinity and limited specificity. (asahq.org)
  • Our initial studies in vitro demonstrate enhanced binding of the compounds to the sodium channel and increased inhibition of prostate cancer cell growth in culture and in soft agarose compared with phenytoin. (elsevier.com)
  • I am particularly interested in voltage-gated sodium channels and my research focuses on (i) characterising receptor sites on sodium channels that bind insecticidal compounds and (ii) understanding how mutations of sodium channels can produce human pain disorders. (ljmu.ac.uk)
  • Cummins TR, Sheets PL, Waxman SG (2007) The roles of sodium channels in nociception: implications for mechanisms of pain. (springer.com)
  • eLife has published papers on topics related to the molecular structure and functional mechanisms of a diverse array of ion channel proteins. (elifesciences.org)
  • This collection highlights a series of important papers that delve into fundamental questions concerning the structure, mechanisms and physiological roles of a diverse array of ion channel proteins. (elifesciences.org)
  • Modified forms of this toxin bearing cysteine-reactive maleimide groups are available through total synthesis and are found to irreversibly inhibit sodium ion conductance in recombinantly expressed wild-type sodium channels and in hippocampal nerve cells. (nih.gov)
  • They also facilitate opening of K+ channels (causing hyperpolarization) and inhibit opening of Ca2+ channels (inhibiting neurotransmitter release). (brainscape.com)
  • Resveratrol analogs and their use to inhibit Kv1.5 channels are provided. (sumobrain.com)
  • This is because lidocaine selectively blocks Na channels in their open and inactive states and has little binding capability in the resting state. (wikipedia.org)
  • Two classes of blocker were used: a) Local anaesthetics (lidocaine and procaine) and (b) blockers of persistent current (INaP) (ranolazine and riluzole). (bl.uk)
  • Metaflumizone perfusion at a hyperpolarized holding potential also shifted the conductance-voltage curve for activation in the direction of depolarization and antagonized use-dependent lidocaine inhibition of fast-inactivated sodium channels, actions not previously observed with other SCI insecticides. (aspetjournals.org)
  • μ-conotoxin SmIIIA toxin has much higher affinity for tetrodotoxin-sensitive Na v channels, including Na v 1.1, Na v 1.2, Na v 1.3, and Na v 1.4. (guidetopharmacology.org)
  • It is a tetrodotoxin-sensitive Na(+) channel isoform (PubMed:7720699). (proteopedia.org)
  • It has long been known that sodium channel blockers are anaesthetics as well as powerful analgesics when delivered at low concentrations. (eurekaselect.com)
  • Voltage-gated sodium channels (Na v s), which are coupled to synaptic vesicle exocytosis, are inhibited by volatile anesthetics through reduction of peak current and modulation of gating. (nih.gov)
  • SCN2B_HUMAN ] Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. (proteopedia.org)
  • Carbamazepine (Carbatrol) is a sodium channel blocker with IC50 of 131 μM in rat brain synaptosomes. (selleckchem.com)
  • Carbamazepine inhibits the binding of [ 3 H]batrachotoxinin A 20-α-benzoate (BTX-B) to a receptor site of voltage-sensitive sodium channel with IC50 of 131 μM, to decrease the activation of sodium channel ion flux in rat brain synaptosomes. (selleckchem.com)
  • Carbamazepine inhibits voltage-gated Na+ channels, stabilizing the inactive conformation of the channel. (lktlabs.com)
  • Carbamazepine also potentiates GABA receptor signaling and inhibits ATP-sensitive K+ channels. (lktlabs.com)
  • Carbamazepine inhibits ATP-sensitive potassium channel activity by disrupting channel response to MgADP. (lktlabs.com)
  • The class I effects (on sodium channels) are rate dependent, which in conjunction with the class III effects (on potassium channels) may increase APD and reduce V max ( Pallandi and Campbell, 1987 ). (frontiersin.org)
  • PHT is a hydantoin-derivative anticonvulsant that exerts its anticonvulsant properties by stabilizing neuronal cell membranes to the action of sodium, potassium, and calcium. (pubmedcentralcanada.ca)
  • When a neuron is at rest, potassium channels are the main type of ion channel that are open. (jove.com)
  • Another transmembrane protein, the sodium potassium pump, uses energy to continuously move sodium out of the cell, and potassium in. (jove.com)
  • In the early 1990s, researchers began looking at potassium channel openers for seizure control. (psychiatrictimes.com)
  • Over the past 10 years, in vitro research and animal studies demonstrated that potassium channel openers could control seizure activity in a dose-dependent way. (psychiatrictimes.com)
  • The potassium channel opener retigabine, currently in phase 3 clinical trials, 'works through the KCNQ-now called Kv7-channels, which modulate the M current, affecting cell excitability,' Porter explained. (psychiatrictimes.com)
  • These voltage-dependent potassium channels turn on during the period of excessive hyperexcitability of the neuron. (psychiatrictimes.com)
  • This was a very surprising finding because until this time, no drug used to treat epilepsy had been found to open potassium channels,' commented Rogawski. (psychiatrictimes.com)
  • Then, Tatulian and colleagues 9 showed that retigabine specifically targeted the KCNQ2/3 potassium channels, which were recognized as playing a key role in familial neonatal convulsions. (psychiatrictimes.com)
  • Voltage-gated potassium (K V ) channels, first identified as the gene encoding the Shaker mutation in the fruit fly Drosophila , exemplify the second structural architecture in the ion channel superfamily. (aspetjournals.org)
  • The inwardly rectifying potassium channels comprise the simplest structural motif in the ion channel protein superfamily. (aspetjournals.org)
  • One of the best known potassium sparing diuretics - amiloride - blocks the action of so-called epithelial sodium channels (ENaCs), which have diverse physiological functions. (phys.org)
  • Our data identify VSD-I as a specific binding site for neurotoxins on sodium channels. (ugent.be)
  • I investigate the structure and function of ion channel membrane proteins and study how they interact with drugs, toxins and environmental pollutants. (ljmu.ac.uk)
  • We also recapitulate the role of Nav1.8 for peripheral pain processing and of additional sodium channelopathies which have been linked to disorders with pain as a significant component. (springer.com)
  • Metaflumizone is a new insecticide for the treatment of fleas on domesticated pets and has recently been reported to block insect sodium channels in the slow-inactivated state, thereby implying that it is also a member of the SCI class. (aspetjournals.org)
  • Thus, SCI insecticides seem to selectively bind to and stabilize sodium channels in a slow-inactivated state. (aspetjournals.org)
  • A standardized nomenclature for sodium channels is currently used and is maintain by the IUPHAR . (wikidoc.org)
  • Nomenclature and structure-function relationships of voltage-gated sodium channels. (springer.com)
  • We conclude that metaflumizone selectively inhibits slow-inactivated Na v 1.4 channels and shares DIV-S6 binding determinants with other SCI insecticides and therapeutic drugs. (aspetjournals.org)
  • The development of sub-type specific blockers has proved slower than anticipated, although the properties of naturally occurring toxin blockers suggest that subtype-specific blockers of sodium channels could be very useful clinically in the treatment of pain. (eurekaselect.com)
  • Our findings support a mechanism for covalent protein modification in which toxin binding to the channel pore precedes maleimide alkylation of a nucleophilic amino acid. (nih.gov)
  • Spider toxin inhibits gating pore cur. (ugent.be)
  • Voltage-gated ion channels are implicated in the regulation of synaptic transmission, muscle contraction and hormone secretion in response to membrane depolarization. (duhnnae.com)
  • The functional elements of the ion channel superfamily of proteins can be divided into three complementary aspects: ion conductance, pore gating, and regulation. (aspetjournals.org)
  • Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity). (proteopedia.org)
  • MuO-conotoxin MrVIB is a blocker of voltage-gated sodium channels, including TTX-sensitive and -resistant subtypes. (nih.gov)
  • We show for the first time that synthetic MrVIB blocks rat NaV1.8 sodium channels and has potent and long-lasting local anesthetic effects when tested in two pain assays in rats. (nih.gov)
  • 4-7 Despite abundant phenomenologic reports that ketamine possesses local anesthetic-like properties, the exact mechanism of the interaction between ketamine and voltage-gated sodium channels is unknown. (asahq.org)
  • Nine voltage-gated sodium (NaVs) channels are expressed in complex patterns in mammalian nerve and muscle. (uclb.com)
  • Lamotrigine is known to block sodium channels but it is not known whether it is extracellular or intracellular. (wikipedia.org)
  • Channels in the deactivated state are thought to be blocked on their intracellular side by an "activation gate", which is removed in response to stimulation that opens the channel. (wikidoc.org)
  • One additional Protoxin-II sits on top of the S3-S4 linker in VSDIV The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. (proteopedia.org)
  • Sodium channel disruptions, such as mutations in SCN2A , may play an important role in psychiatric disorders. (biomedcentral.com)
  • They often require transmembrane proteins, such as ion channels, to allow them to pass through. (jove.com)
  • A family of proteins (OSCA/TMEM63) that encode mechanosensitive ion channels has been characterized in plants, flies, and mammals. (elifesciences.org)
  • The primary cilia polycystin proteins, polycystin-1 and polycystin-2, affect cilia length in the kidney collecting duct epithelia, but only polycystin-2 is required for the functional ion channel in this organelle. (elifesciences.org)
  • TMEM206 proteins are identified as constituting the pore of the widely expressed acid-activated chloride channel PAORAC/ASOR, which is important in acid toxicity. (elifesciences.org)
  • Background and Aims Vixotrigine is a state- and use-dependent voltage-gated sodium channel blocker under investigation for treatment of neuropathic pain. (eventscribe.com)
  • Scientists at University College London have developed Voltage-Gated Sodium Channel subtype specific conditional knockout mice which provide invaluable tools for the development of therapeutics for the treatment of pain. (uclb.com)
  • The channel subtype specific knockout mice developed at University College London provide an invaluable tool to support such efforts. (uclb.com)
  • Of the sodium channel blocking antiarrhythmic agents (the class I antiarrhythmic agents), the class Ic agents have the most potent sodium channel blocking effects. (wikipedia.org)
  • Our results establish that the preferred disulfide pattern of synthetic mu-KIIIA and mu-KIIIB folded in vitro is 1-5/2-4/3-6 but that other disulfide isomers are also potent sodium channel blockers. (monash.edu)
  • NaV1.8 Cre'-Transgenic mouse expressing Cre-recombinase gene under the control of the NaV1.8 sodium channel gene promoter (as described in Stirling et al. (uclb.com)
  • As the quest for new selective molecules targeting sodium channels for the treatment of chronic pain continues, Axon Medchem intends to expand its range of sodium channel modulators accordingly. (axonmedchem.com)
  • [3] [ SCN9A_HUMAN ] Mediates the voltage-dependent sodium ion permeability of excitable membranes. (proteopedia.org)
  • Long-term treatments with AMD is suggested to induce remodeling of ion-channel expression in a dose-dependent manner, leading to electrophysiological variations. (frontiersin.org)
  • We also directly investigated the ketamine anesthetic binding site through expression of a mutant channel. (asahq.org)
  • Sodium channel expression in oocytes requires coinjection with β 1 to duplicate in vivo channel function. (asahq.org)
  • For example, we have recently investigated changes in expression of voltage gated sodium channels under inflammatory and post-incisional conditions. (stanford.edu)
  • The expression of voltage-gated sodium channels (VGSCs) was recently associated with the metastatic behavior of prostate cancer cells. (elsevier.com)
  • Ligand gated sodium channels (e.g. nicotinic receptors ) are activated by endogenous acetylcholine. (axonmedchem.com)
  • Consistent with previous investigations of SCI insecticides on rat Na v 1.4 channels, the F1579A mutation reduced sensitivity to block by metaflumizone, whereas the Y1586A mutation paradoxically increased the sensitivity to metaflumizone. (aspetjournals.org)
  • Class Ia agents block the fast sodium channel, which depresses the phase 0 depolarization (i.e. reduces V max ), which prolongs the action potential duration by slowing conduction. (wikipedia.org)
  • Focal microinjection of tetrodotoxin (TTX), a potent voltage-gated sodium channel blocker, reduces neurological deficits and tissue loss after spinal cord injury (SCI). (jneurosci.org)
  • In the kidney, the so-called alpha/beta/gamma subtype is involved in the resorption of sodium from the urine, which reduces water loss and maintains blood volume. (phys.org)
  • Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. (springer.com)