A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.
Cell membrane glycoproteins that 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.
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.
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.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.
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.
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.
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.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
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).
Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized.
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.
Pyridines substituted in any position with an amino group. May be hydrogenated, but must retain at least one double bond.
A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.
Venoms obtained from Apis mellifera (honey bee) and related species. They contain various enzymes, polypeptide toxins, and other substances, some of which are allergenic or immunogenic or both. These venoms were formerly used in rheumatism to stimulate the pituitary-adrenal system.
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.
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.
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.
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.
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.
Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.
Potassium channels whose activation is dependent on intracellular calcium concentrations.
A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.
A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.
The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
A 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.
Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.
A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)
A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.
Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A voltage-gated potassium channel that is expressed primarily in the HEART.
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.
Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.
A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A 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.
Venoms produced by the wasp (Vespid) family of stinging insects, including hornets; the venoms contain enzymes, biogenic amines, histamine releasing factors, kinins, toxic polypeptides, etc., and are similar to bee venoms.
Venoms from SNAKES of the viperid family. They tend to be less toxic than elapid or hydrophid venoms and act mainly on the vascular system, interfering with coagulation and capillary membrane integrity and are highly cytotoxic. They contain large amounts of several enzymes, other factors, and some toxins.
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
A 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.
A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.
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.
Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.
Potassium channels that contain two pores in tandem. They are responsible for baseline or leak currents and may be the most numerous of all K channels.
A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is closely related to KCNQ2 POTASSIUM CHANNEL. It is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
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.
Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.
A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.
The 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.
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 group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.
Drugs used to cause dilation of the blood vessels.
Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The ability of a substrate to allow the passage of ELECTRONS.
Venoms from animals of the phylum Arthropoda. Those most investigated are from scorpions and spiders of the class Arachnidae and from ant, bee, and wasp families of the Insecta order Hymenoptera. The venoms contain protein toxins, enzymes, and other bioactive substances and may be lethal to man.
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.
Use of electric potential or currents to elicit biological responses.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
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.
Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)
A family of hexahydropyridines.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)
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.
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.
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.
CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
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.
The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The rate dynamics in chemical or physical systems.
Inorganic compounds that contain barium as an integral part of the molecule.
ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.
A genus of poisonous snakes of the VIPERIDAE family. About 50 species are known and all are found in tropical America and southern South America. Bothrops atrox is the fer-de-lance and B. jararaca is the jararaca. (Goin, Goin, and Zug, Introduction to Herpetology, 3d ed, p336)
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.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Potassium or potassium compounds used in foods or as foods.
Antisera used to counteract poisoning by animal VENOMS, especially SNAKE VENOMS.
Compounds with a core of fused benzo-pyran rings.
A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.
Venoms produced by FISHES, including SHARKS and sting rays, usually delivered by spines. They contain various substances, including very labile toxins that affect the HEART specifically and all MUSCLES generally.
10-carbon saturated monocarboxylic acids.
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.
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.
Venoms from the superfamily Formicoidea, Ants. They may contain protein factors and toxins, histamine, enzymes, and alkaloids and are often allergenic or immunogenic.
A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.
Organic compounds containing both the hydroxyl and carboxyl radicals.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A family of extremely venomous snakes, comprising coral snakes, cobras, mambas, kraits, and sea snakes. They are widely distributed, being found in the southern United States, South America, Africa, southern Asia, Australia, and the Pacific Islands. The elapids include three subfamilies: Elapinae, Hydrophiinae, and Lauticaudinae. Like the viperids, they have venom fangs in the front part of the upper jaw. The mambas of Africa are the most dangerous of all snakes by virtue of their size, speed, and highly toxic venom. (Goin, Goin, and Zug, Introduction to Herpetology, 3d ed, p329-33)
Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.
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.
A derivative of the NIACINAMIDE that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase.
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.
A condition due to decreased dietary intake of potassium, as in starvation or failure to administer in intravenous solutions, or to gastrointestinal loss in diarrhea, chronic laxative abuse, vomiting, gastric suction, or bowel diversion. Severe potassium deficiency may produce muscular weakness and lead to paralysis and respiratory failure. Muscular malfunction may result in hypoventilation, paralytic ileus, hypotension, muscle twitches, tetany, and rhabomyolysis. Nephropathy from potassium deficit impairs the concentrating mechanism, producing POLYURIA and decreased maximal urinary concentrating ability with secondary POLYDIPSIA. (Merck Manual, 16th ed)
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.
Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.
Benzoic acid or benzoic acid esters substituted with one or more nitro groups.
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.
Inorganic compounds that contain potassium as an integral part of the molecule.
Established cell cultures that have the potential to propagate indefinitely.
The regulatory subunits of large-conductance calcium-activated potassium channels.
A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.
Limbless REPTILES of the suborder Serpentes.
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.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
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.
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.
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 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 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.
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 species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.
A 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 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.
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.
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 long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.
An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells.
Stable potassium atoms that have the same atomic number as the element potassium, but differ in atomic weight. K-41 is a stable potassium isotope.
A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.
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.
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.
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)
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.
The nonstriated involuntary muscle tissue of blood vessels.
A delayed rectifier subtype of shaker potassium channels that has been described in NEURONS and ASTROCYTES.
CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
The hollow, muscular organ that maintains the circulation of the blood.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
A 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 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.
Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
Compounds with a BENZENE fused to IMIDAZOLES.
A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)
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.
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)
A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)
A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.
An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.
Venoms produced by frogs, toads, salamanders, etc. The venom glands are usually on the skin of the back and contain cardiotoxic glycosides, cholinolytics, and a number of other bioactive materials, many of which have been characterized. The venoms have been used as arrow poisons and include bufogenin, bufotoxin, bufagin, bufotalin, histrionicotoxins, and pumiliotoxin.
Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.
A genus of venomous snakes of the subfamily Crotalinae. Twelve species of this genus are found in North and Central America and Asia. Agkistrodon contortrix is the copperhead, A. piscivorus, the cottonmouth. The former is named for its russet or orange-brown color, the latter for the white interior of its mouth. (Goin, Goin, and Zug, Introduction to Herpetology, 3d ed, p336; Moore, Poisonous Snakes of the World, 1980, p75)
A family of neuronal calcium-sensor proteins that interact with and regulate potassium channels, type A.
A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.
A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.
CALCIUM CHANNELS located in the neurons of the brain.
A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.
A 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)
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
An inhibitor of anion conductance including band 3-mediated anion transport.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.
An actinomycete used for production of commercial ANTIBIOTICS and as a host for gene cloning.
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.
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.
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)
Proteins prepared by recombinant DNA technology.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
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 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.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
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 group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)
Agents that promote the excretion of urine through their effects on kidney function.
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.
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)
Bougis, PE; Martin-Eauclaire, MF (25 June 2015). "Shal-type (Kv4.x) potassium channel pore blockers from scorpion venoms". ... Martin-Eauclaire, MF; Bougis, PE (2012). "Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus ... The toxin is known for its ability to act as a specific Kv4 channel blocker, and thereby reducing the A-type potassium current ... By blocking specifically the Kv4 channels, AmmTX3 reduces the A-type potassium current through these channels almost completely ...
"A potent potassium channel blocker from Mesobuthus eupeus scorpion venom". Biochimie. 92 (12): 1847-1853. doi:10.1016/j.biochi. ... This short-chain peptide blocks potassium channels, such as Kv1.1, Kv1.2 and Kv1.3. MeuKTX is a neurotoxin found in the venom ... Typically, α-KTxs affect voltage-gated potassium channels. MeuKTX is a potent partial blocker for rat Kv1.1 (rKv1.1), rKv1.2, ... and human Kv1.3 (hKv1.3). The effectiveness of MeuKTX as a blocker for these potassium channels is summarized below: Complete ...
Gao, B; Peigneur, S; Tytgat, J; Zhu, S (2010). "A potent potassium channel blocker from Mesobuthus eupeus scorpion venom". ... In contrast, BeKm-1 specifically inhibits hERG channels, which are potassium channels critical to maintaining normal electrical ... but showed no effects on various other potassium channels tested. Inhibitors of sodium channels have also been found in this ... As in other scorpions, the venom of M. eupeus contains various neurotoxic proteins that interact specifically with ion channels ...
OdK2, a potassium channel blocker present in the venom of Odontobuthus doriae. "BioLib - Odontobuthus doriae". biolib.cz. ... 19, p. 75-272 Vatanpour, Hossein · Jalali, Amir G Rowan, Edward · Rahim, Fakher Effects of odontobuthus doriae scorpion venom ...
"Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus". Toxicon. 119: 253-265. doi:10.1016/j. ... It seems likely that TsPep2 has inhibitory actions on potassium channels, based on its sequence similarities in the C-terminal ... TsPep2 is identified from the venom of Tityus serrulatus by using a cDNA primer sequence based on the C-terminal amino acid ... beta sheet with the potassium channel inhibitory alpha family (α-KTX) and on its similarities in the patterns of disulfide ...
The venom of this spider contains the toxin HpTX2, a potassium channel blocker. In some tropical areas the spider is considered ... 2000). Solution structure of hpTX2, a toxin from Heteropoda venatoria spider that blocks Kv4.2 potassium channel. Protein ... After capturing its prey, the spider injects them with venom. ... but it does deliver enough venom to give a painful bite. The ...
The potassium channel blocker tetraethylammonium (TEA) has been shown to reverse the effects of tubocurarine. It is thought to ... The venom is the most damaging to nerve endings, but the introduction of d-tubocurarine chloride blocks the nAChr, alleviating ... Spiders of the genus Latrodectus have α-latrotoxin in their venom. The most well known spider in this genus is the black widow ... "d-Tubocurarine (Prototype Nondepolarizing Neuromuscular Blocker)". Tulane University. Retrieved 4 May 2015. Bowman WC, Webb SN ...
In addition, it is a potent blocker of voltage-sensitive potassium channels. MCD peptide is a component of bumblebee ( ... melittin and apamin have also been identified in this venom and are also described as voltage-dependent channel blockers. MCD ... It binds to several subclasses of voltage-gated potassium channels (Kv channels), including Kv1.1, Kv1.6, and less potently to ... By blocking potassium channels, the MCD peptide can increase the duration of action potentials and increase neuronal ...
This toxin is a selective blocker of BK channels, calcium-activated potassium channels. Limbatustoxin is purified from the ... peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus". Journal ... also called maxi-K channels, slo1 or BK (big potassium) channels. These channels play an important role in the excitability of ... Yu, M, Liu, SL, Sun, PB, Pan, H, Tian, CL, & Zhang, LH (2016). "Peptide toxins and small-molecule blockers of BK channels". ...
... a new potassium channel blocker from the venom of chinese scorpion Buthus martensi Karsch". Proteins. 55 (4): 835-45. doi: ... They include a novel short-chain peptide from the Asian scorpion Mesobuthus martensii Karsch, a potassium channel blocker ... a novel potassium channel-blocking peptide, from the venom of Asian scorpion Buthus martensi Karsch". Toxicon. 43 (8): 895-900 ... It has a lower activity towards Kv channels and it is predicted that it may prefer a type of SK channel with a narrower ...
BeKm-1 shows structural homology to the family of scorpion venom potassium channel blockers, the α-KTx family. Despite the ... which are voltage gated potassium ion channels. Be is the abbreviation of the scorpion from which the venom is isolated, Buthus ... BekM-1 selectively inhibits hERG potassium channels that are coded by the human ether-a-go-go-related gene. By toxin ... The hERG channels are prominently expressed in myocytes; inhibition of these channels by BekM-1 prolongs the QT interval in the ...
A Novel Potassium Channel Blocker from the Venom of the Indian Red Scorpion Mesobuthus tamulus". Archives of Biochemistry and ... potassium channels in the heart and calcium activated potassium channels. Within this family, TmTx belongs to the α-KTx 16 ... calcium-activated potassium channel), respectively. Another suggested target is the Kv1.6 channel, a voltage-gated potassium ... It belongs to the group of alpha potassium toxins (α-KTx: alpha toxin affecting potassium channels). This group contains short- ...
Its venom contains highly specific potassium channel blockers such as iberiotoxin, which is a highly specific blocker of the ... a novel potassium channel blocker from the venom of the Indian red scorpion Mesobuthus tamulus". Arch. Biochem. Biophys. 385 (1 ... This specific channel block evokes a reduction in the small conductance calcium-dependent potassium channels current. Previous ... A less closely related member of the SK channels is the intermediate conductance calcium activated potassium channel SK4, also ...
By acting as a specific pore-blocker of Kv4.3 potassium channels, AaTX1 inhibits the IA current through these channels. As a ... thereby abolishing the A-type potassium currents. AaTX1 is a peptide that can be purified from the venom of Androctonus ... typically found in pore-blocking potassium channel-specific toxins. AaTX1 is a specific pore-blocker of Kv4.3 potassium ... The toxin acts as a specific blocker on Kv4.3 voltage-gated potassium channel, ...
They are selective blockers of voltage-gated potassium channels The source for the pandinotoxins is the venom of the scorpion ... a Selective Blocker of A-Type Potassium Channels". Biochemistry. 36: 2763-71. doi:10.1021/bI9628432. PMID 9062103. Rogowski RS ... Pandinotoxins are the most potent inhibitors of the rapidly inactivating A-type voltage-gated potassium channels. They also ... and they can reversibly block the shaker B potassium-channels (Kv1.1 sub-family). The residue K27, a lysine at place 27 of the ...
... a new potassium channel blocker from the venom of the Chinese scorpion Buthus martensi Karsch". Biochemistry. 39 (45): 13669-75 ... Zhu L, Gao B, Luo L, Zhu S (March 2012). "Two dyad-free Shaker-type K⁺ channel blockers from scorpion venom". Toxicon. 59 (3): ... BmP05 acts blocks the Ca2+-activated K+ channel (SKCa), whereas BmP02 acts on potassium channels, but is not able to exert a ... BmP02 targets potassium channels. Its activity has been shown in Kv1.1-Kv1.3, Kv4.2, Shaker-IR (Inactivation Removed) type, and ...
"Compared toxicity of the potassium channel blockers, apamin and dendrotoxin". Toxicology. 104 (1-3): 47-52. doi:10.1016/0300- ... Dry bee venom consists of 2-3% of apamin. Apamin selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed ... Here it inhibits small-conductance Ca2+-activated K+ channels (SK channels) in neurons. These channels are responsible for the ... SK channel blockers may have a therapeutic effect on Parkinson's disease. Dopamine, which is depleted in this disease, will be ...
The Tst26 toxin is a voltage-gated potassium channel blocker present in the venom of Tityus stigmurus, a species of Brazilian ... Tst26 selectively blocks Kv1.2 and Kv1.3 voltage gated potassium channels and has high affinity to both channels. It has an ... a novel peptide blocker of Kv1.2 and Kv1.3 channels from the venom of Tityus stigmurus". Toxicon. 54 (4): 379-389. doi:10.1016/ ... activation or inactivation of the potassium channels but did slow down the inactivation of Kv1.3 channels. "UniProtKB - P0CB56 ...
... is a "short-chain" peptide like other potassium channel blockers in the scorpion venom and added to the phylogenetic tree ... It blocks A-type potassium channels in the central nervous system and hERG-channels in the heart. BmTx3 was originally purified ... As BmTx3 seems to use both sides to bind to different potassium channels, it might be an evolutionary transient between the two ... BmTx3 blocks primarily the Kv4.x proteins and has a higher affinity for Kv4.1 channels than for Kv4.2 and Kv4.3 channels. The ...
It is a potent blocker of voltage-gated potassium channel, Kv1.3 and is closely related to another peptide found in the venom, ... The Pi3 toxin is a potent inhibitor of the Kv1.2 potassium channel, encoded by the KCNA2 gene and a less potent blocker of ... Both Pi3 and Pi2 are considered to belong to the pore blocker family. Pore blockers bind to pore of the ion channel and block ... The human homologues of shaker B channels are the Kv1 channels. The affinity of the Pi3 for shaker B voltage- gated potassium ...
... which had been found previously and which is also a potassium channel blocker. Lq2 is a component of the venom of the scorpion ... Since all potassium channels share the same ion conducting outer pore structure, Lq2 binds to all three potassium channel types ... It blocks various potassium channels, among others the inward-rectifier potassium ion channel ROMK1. Lq2 is also known as ... especially the Renal Outer Medullary Potassium channel ROMK1. This ion channel contributes to the regulation of the resting ...
Tst26, a potassium channel blocker present in the venom of Tityus stigmurus Binomial authority Description Diet and pet housing ... Venom extraction kits were tested and proven to be ineffective in mitigating or preventing envenomation and causes more tissue ...
... (MgTX) is a peptide that selectively inhibits Kv1.3 voltage-dependent potassium channels. It is found in the venom ... Margatoxin is classified as a "scorpion short toxin" by Pfam, showing sequence homology with other potassium channel blockers, ... Potassium channels are required for the activation of T-cells. Pharmacological inhibition of Potassium channels can be useful ... Margatoxin blocks potassium channels Kv1.1 Kv1.2 en Kv1.3. Kv1.2 channel regulates neurotransmitter release associated with ...
... a type of voltage-gated potassium channel, and as a blocker of voltage-gated sodium channels, including Nav1.2 and Nav1.8. ... The scorpion venom ErgTx also targets the hERG channel. However, ErgTx has only a 20% sequence homology with APETx1. APETx1 ... Ding XW, Yan JJ, An P, Lü P, Luo HS (February 2007). "Aberrant expression of ether à go-go potassium channel in colorectal ... inhibits the hERG channel, a type of voltage-gated potassium channel. APETx1 is thought to interact with three aromatic ...
This neurotoxin belongs to the alpha family of potassium channel acting peptides. It is a high-affinity blocker of Kv1.3 ... Anuroctoxin (α-KTx 6.12) is a peptide from the venom of the Mexican scorpion Anuroctonus phaiodactylus. ... potassium channels. Anuroctoxin does not block any of the following channels: calcium-activated KCa3.1/KCNN4 potassium channels ... Shaker IR, Kv1.1/KCNA1, and Kv2.1/KCNB1 potassium channels. The α-KTx inhibition of the potassium channels is mediated by a ...
... activated K+ channels characterized from Androctonus mauretanicus mauretanicus venom". Journal of Biological Chemistry. 267 (3 ... Potassium channel blockers are agents which interfere with conduction through potassium channels. Potassium channel blockers ... Sulfonylureas, such as gliclazide, are ATP-sensitive potassium channel blockers. Dalfampridine, A potassium channel blocker has ... Examples of voltage-gated channel blockers include: Linopirdine XE-991 Spooky toxin (SsTx) Potassium channel Potassium channel ...
... calcicludine has no effect on dendrotoxin-sensitive potassium channels in chicken and rat neurons. Calcicludine is a blocker of ... Calcicludine (CaC) is a protein toxin from the venom of the green mamba that inhibits high-voltage-activated calcium channels, ... is a potent blocker of high-threshold Ca2+ channels with a high affinity for L-type channels in cerebellar granule neurons". ... high-voltage-activated calcium channels (L-, N- and P-type channels). It has highest affinity to the L-type calcium channel ( ...
... whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. Mu- ... an N-type neuronal calcium channel blocker found in the venom of Conus magus". Toxicon. 36 (11): 1651-1658. doi:10.1016/S0041- ... κ-conotoxin inhibits potassium channels. μ-conotoxin inhibits voltage-dependent sodium channels in muscles. ω-conotoxin ... "Conus venoms: a rich source of novel ion channel-targeted peptides". Physiol. Rev. 84 (1): 41-68. doi:10.1152/physrev. ...
Above a certain level of potassium the depolarization inactivates sodium channels, opens potassium channels, thus the cells ... Therefore, beta blockers can raise potassium levels by blocking beta-2 receptors. However, the rise in potassium levels is not ... Box jellyfish venom can also cause hyperkalemia. Excessive intake of potassium is not a primary cause of hyperkalemia because ... There appears to be a direct effect of elevated potassium on some of the potassium channels that increases their activity and ...
HS-1 is likely to be a voltage-gated potassium channel blocker. HS-1 also has antimicrobial effects on some bacterial species, ... 2013). "Scorpion venom components that affect ion-channels function". Toxicon. 76 (1): 328-342. doi:10.1016/j.toxicon.2013.07. ... 2013). "Scorpion venom components that affect ion-channels function". Toxicon. 65 (1): 187-200. doi:10.1007/s00018-007-7370-x. ... It is a polypeptide consisting of a defensin-like component on its N-terminal end and a putative potassium channel blocking ...
鉀離子通道阻滯劑(英語:Potassium channel blocker) (PCB) ... Venomous Animals and Their Venoms: Venomous Vertebrates. Elsevier. 2013: 478 [2016-03-19]. ISBN 9781483262888. (原始內容存檔於2016-03- ... 腎上腺素受體拮抗劑 (α(英語:Alpha blocker) (1(英語:Alpha-1 blocker) ...
Uncompetitive NMDA receptor antagonists, or channel blockers, enter the channel of the NMDA receptor after it has been ... consists of three transmembrane segments and a re-entrant loop reminiscent of the selectivity filter of potassium channels. ... Argiotoxin-636 - naturally occurring dizocilpine or related site antagonist found in Argiope venom ... Memantine is an example of an uncompetitive channel blocker of the NMDA receptor, with a relatively rapid off-rate and low ...
Above a certain level of potassium the depolarization inactivates sodium channels, opens potassium channels, thus the cells ... beta blockers can cause the rise in potassium levels due to blockage of beta-2 receptors. However, the rise potassium levels is ... Box jellyfish venom can also cause hyperkalemia.[21] ... effect of elevated potassium on some of the potassium channels ... Exercise can cause a release of potassium into bloodstream by increasing the number of potassium channels in the cell membrane ...
... a Selective Blocker of A-Type Potassium Channels". Biochemistry. 36: 2763-71. doi:10.1021/bI9628432. PMID 9062103.. ... Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker ... and iberiotoxin with potassium channels: selectivity between voltage-gated and Maxi-K channels". Proteins. 52 (2): 146-54. doi: ... "Mechanisms of maurotoxin action on Shaker potassium channels". Biophys. J. 79 (2): 776-87. doi:10.1016/S0006-3495(00)76335-1. ...
Other ion channels can also be disrupted, such as the potassium channels causing inefficient repolarization at the presynaptic ... Most commonly animal venom or poison, or other toxic substances are the origin of the problem. ... These include overuse of anticholinesterase drugs, high-dose prednisone, and anesthesia and neuromuscular blockers for ... Neuromyotonia causes antibodies to damage the normal function of potassium rectifier channels, while Lambert-Eaton syndrome ...
... is a sodium channel blocker. It inhibits the firing of action potentials in neurons by binding to the voltage- ... This is the first reported case in which tetrodotoxin has been found to occur in a venom.. ... the oral LD50 of potassium cyanide for mice is 8.5 mg per kg,[40] demonstrating that even orally, TTX is more poisonous than ... channels) and tetrodotoxin-resistant voltage-gated sodium channels (TTX-r Na+ channels). Tetrodotoxin inhibits TTX-s Na+ ...
... is a potassium channel blocker. Paxilline is a toxic, tremorgenic indole alkaloid produced by Penicillium paxilli . ... "Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K(alpha) and pandinustoxin-K( ... Sheehan, JJ; Benedetti, BL; Barth, AL (2009). "Anticonvulsant effects of the BK-channel antagonist paxilline". Epilepsia. 50: ...
G. spatulata) venom. It inhibits the drk1 voltage-gated potassium channel by altering the energetics of gating. See also ... consensus molecular folding of calcium channel blockers". J. Mol. Biol. 250 (5): 659-71. doi:10.1006/jmbi.1995.0406. PMID ... Spider potassium channel inhibitory toxins is another group of spider toxins. A representative of this group is hanatoxin, a 35 ... A remotely related group of atracotoxins operate by opening sodium channels. δ-Atracotoxin from the venom of the Sydney funnel- ...
These structures patterns suggest that ImKTx88 may be a potential Kv channel blocker for its similarity with Kv channel blocker ... ImKTx88 is a selective inhibitor of the Kv1 ion channel family that can be isolated from the venom of the Isometrus maculatus ( ... "Potassium channel toxin ImKTx88 precursor - Isometrus maculatus (Lesser brown scorpion)". www.uniprot.org. Retrieved 2017-10-09 ... "Potassium channels Kv1.3 and Kv1.5 are expressed on blood-derived dendritic cells in the central nervous system". Annals of ...
... is a weak blocker of the high potassium-induced contraction of smooth muscles. Snake venom CRISP family proteins ... suggesting that it inhibits voltage-dependent calcium channels. The toxin was named ophanin after the snake whose venom it is ... "Wide distribution of cysteine-rich secretory proteins in snake venoms: isolation and cloning of novel snake venom cysteine-rich ... The LD50 of the venom in mice is ~1.2 to 3.5 mg/kg via intravenous injection. The LD50 of ophanin is not yet known. Other snake ...
Some potassium channels: Inward-rectifier potassium channels: These channels allow potassium ions to flow into the cell in an " ... A variety of ion channel blockers (inorganic and organic molecules) can modulate ion channel activity and conductance. Some ... the venoms produced by spiders, scorpions, snakes, fish, bees, sea snails, and others) work by modulating ion channel ... Potassium channels Voltage-gated potassium channels e.g., Kvs, Kirs etc. Calcium-activated potassium channels e.g., BKCa or ...
... peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus". The ... Candia, S; Garcia, ML; Latorre, R (1992). "Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)- ... Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels (maxiK or BK channels) with ... It is also known as "Potassium channel toxin alpha-KTx 1.3" or IbTx. The complete amino acid sequence has been defined and it ...
Swartz, K.J.; MacKinnon, R. (1995). "An Inhibitor of the Kv2.1 Potassium Channel Isolated from the Venom of a Chilean Tarantula ... Herrington, J. e.a. (2006). "Blockers of the Delayed-Rectifier Potassium Current in Pancreatic β-Cells Enhance Glucose- ... The potassium channels that hanatoxin inhibits have huge diversity and are involved in a number of functions such as regulation ... The venom is lethal to smaller animals like mice: 0.1 ml of the venom is lethal to mice within about 5 min (Escoubas & Rash ...
... this differential effect indicates that piscivorin is an L-type calcium channel blocker. At a concentration of 1 μM, its effect ... "Wide distribution of cysteine-rich secretory proteins in snake venoms: Isolation and cloning of novel snake venom cysteine-rich ... Piscivorin reduces high potassium-evoked smooth muscle contraction, but does not inhibit caffeine-stimulated contraction of ... Typically, crude venom from the Eastern Cottonmouth contains approximately 1.25% of piscivorin. Piscivorin belongs to the ...
... and SK potassium channels. Pi4 binds to Shaker B potassium channels, the Drosophila homologue of the voltage-gated potassium ... "Two similar peptides from the venom of the scorpion pandinus imperator, one highly effective blocker and the other inactive on ... the Pi4 binds to SK channels, small conductance Ca2+-activated potassium channels. Pi4 competes with apamin, another SK-channel ... Pi4 (α-KTx 6.4) is a short toxin from the scorpion Pandinus imperator that blocks specific potassium channels. The name Pi4 is ...
"Neurotoxins in Snake Venom". Retrieved 2019-12-26. Newitt RA, Houamed KM, Rehm H, Tempel BL. (1991). "[Potassium channels and ... homologous to Kunitz-type proteinase inhibitors with activity as a selective blocker of voltage-gated potassium channels ... binds to potassium channel proteins.]". Epilepsy Research Supplement. 4: 263-73. PMID 1815606.CS1 maint: uses authors parameter ... structure-activity relationships and effects on potassium ion channels". Curr. Med. Chem. 11 (23): 3065-72. doi:10.2174/ ...
These venoms are toxic due to their blocking of calcium channels and also because they reduce potassium-induced smooth muscle ... channel blocker derived from snake venom". Journal of Molecular Biology. 350 (4): 735-43. doi:10.1016/j.jmb.2005.05.020. PMID ... The selective ion channel activity of snake CRISPs, coupled with the variety of CRISPs available as the pool of venom proteins ... ion channel activity occurred by blocking of cyclic nucleotide-gated ion channels. One of the N. haje CRISPs was the first ...
... which is often found with Kv channel blocker toxins. The venom of Pandinus imperator is not lethal to humans. Olamendi-Portugal ... Pi5 inhibits human Kv1.2 and Kv1.3 channels as well as Drosophila Shaker B potassium channels. Pi5 is a peptide that is ... Pi5 inhibits the human voltage-dependent potassium channels Kv1.2 and Kv1.3. These channels are coded respectively by the genes ... KTx is the abbreviation of kaliotoxin, which is a potassium channel toxin. There are three KTx families: α-, β- and γ-KTx. The ...
ICK toxins are best known as blockers of cation channels. The exact structure of the VaTxs has not yet been deduced, although ... VaTx1 and 2 also act as antagonists for the Kv2-type voltage-gated potassium channel (Kv2), inducing paralytic behavior in ... P. cambridgei, a tarantula from Trinidad, uses its venom to paralyze its prey. Amongst other compounds, this venom contains all ... In general, the venom of P. cambridgei is known to produce pain, but the amount of toxin that is present in a bite is too low ...
Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus. Marie-France Martin-Eauclaire and Pierre E ... Marie-France Martin-Eauclaire and Pierre E. Bougis, "Potassium Channels Blockers from the Venom of Androctonus mauretanicus ...
PROTEINASE INHIBITOR HOMOLOGUES AS POTASSIUM CHANNEL BLOCKERS. *DOI: 10.2210/pdb1DEN/pdb. *Classification: VENOM(POTASSIUM ... We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae ... We report here the NMR structure of dendrotoxin I, a powerful potassium channel blocker from the venom of the African Elapidae ... Proteinase inhibitor homologues as potassium channel blockers.. Lancelin, J.M., Foray, M.F., Poncin, M., Hollecker, M., Marion ...
Bougis, PE; Martin-Eauclaire, MF (25 June 2015). "Shal-type (Kv4.x) potassium channel pore blockers from scorpion venoms". ... "Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus". Journal of Toxicology. 2012: 103608. doi: ... The toxin is known for its ability to act as a specific Kv4 channel blocker, and thereby reducing the A-type potassium current ... By blocking specifically the Kv4 channels, AmmTX3 reduces the A-type potassium current through these channels almost completely ...
"A potent potassium channel blocker from Mesobuthus eupeus scorpion venom". Biochimie. 92 (12): 1847-1853. doi:10.1016/j.biochi. ... This short-chain peptide blocks potassium channels, such as Kv1.1, Kv1.2 and Kv1.3. MeuKTX is a neurotoxin found in the venom ... Typically, α-KTxs affect voltage-gated potassium channels. MeuKTX is a potent partial blocker for rat Kv1.1 (rKv1.1), rKv1.2, ... and human Kv1.3 (hKv1.3). The effectiveness of MeuKTX as a blocker for these potassium channels is summarized below: Complete ...
The potassium channel blocker tetraethylammonium (TEA) has been shown to reverse the effects of tubocurarine. It is thought to ... The venom is the most damaging to nerve endings, but the introduction of d-tubocurarine chloride blocks the nAChr, alleviating ... Spiders of the genus Latrodectus have α-latrotoxin in their venom. The most well known spider in this genus is the black widow ... "d-Tubocurarine (Prototype Nondepolarizing Neuromuscular Blocker)". Tulane University. Retrieved 4 May 2015. Bowman WC, Webb SN ...
Venoms to Drugs will find wide readership with researchers working in academia and industry working in all medicinal and ... To date six drugs derived from venom peptides or proteins have been approved by the FDA, with nine further agents currently ... This unique book provides an up to date and comprehensive account of the potential of peptides and proteins from animal venoms ... Topics covered include chemistry and structural biology of animal venoms, proteomic and transcriptomic approaches to drug ...
Kaliotoxin2 (KTX2) is a highly selective blocker of voltage-dependent potassium channels Kv1.3 containing 37 amino acid ... Scorpion venom components that affect ion-channels function. Toxicon. 2013;76:328-42. https://​doi.​org/​10.​1016/​j.​toxicon.​ ... The molecular mechanism of toxin-induced conformational changes in a potassium channel: relation to C-type inactivation. ... Sifi N, Martin-Eauclaire MF, Laraba-Djebari F. K(+) channel blocker-induced neuroinflammatory response and neurological ...
Kinetas lead clinical stage program, ShK-186, is a selective and potent blocker of the voltage-gated Kv1.3 potassium channel. ... Potassium channels regulate cell membrane potential and control a variety of cellular processes. Earlier studies using mice ... Gary V. Desir, professor of medicine at Yale University, and an expert on the Kv1.3 channels role in renal potassium secretion ... a potassium channel gene, suggested that Kv1.3 regulated body weight and the basal metabolic rate. ...
Given the presence of several medically important scorpion species, the study of their venom in the country is also important. ... A graphical representation of the different types of components found in these venoms is also revised. A map with hotspots ... A novel potent blocker of Kv1.3 potassium channels of human T lymphocytes. Biochemistry 2012, 51, 4049-4061. [Google Scholar] [ ... a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels. J. Biol. Chem. ...
A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus. ... Judge, S.; Bever, C. Potassium channel blockers in multiple sclerosis: Neuronal K-V channels and effects of symptomatic ... The inhibition of potassium channels by peptides from animal venoms is a subject of broad interest for its physiological and ... a four disulfide bridge toxin from Scorpio maurus venom: Purification, structure and action on potassium channels. FEBS Lett. ...
Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1: AN INTEGRATED TRANSCRIPTOMIC ... FP-Tx are displaced by other potassium channel blockers and can be used as an imaging tool in ion channel ligand screening ... Based on Tk-AMP-X2 structural similarity to cone snail and scorpion potassium channel blockers, a mutant molecule, Tk-hefu, was ... Here, we report a comprehensive analysis of putative potassium channel toxins (KTxs) from the cDNA library of M. eupeus venom ...
... the study of venomous animals has focused on the isolation and biochemical characterization of specific venom components that ... "Venom Protein Families: Potassium Channels Blockers from Scorpion Venoms"), antimicrobial and cytolytic peptides, are more ... Molecular Description of Scorpion Toxin Interaction with Voltage-Gated Sodium Channels Venom Protein Families: Potassium ... They are (in)famous for the Na+ channel-modulating toxins present in their venoms that are capable of depolarizing the axonal ...
... venom were examined. The isometric contractions of spontaneously beating... ... a novel potassium channel blocker from the venom of the Indian red scorpion Mesobuthus tamulus. Arch Biochem Biophys 385:138- ... peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus. J Biol ... Yatani A, Codina J, Brown AM, Birnbaumer L (1987) Direct activation of mammalian atrial muscarinic potassium channels by GTP ...
... a database for peptide toxins from scorpion venom. It enables scientists to systematize information on ... ... Thus, Kalium covers a large group of molecules that act on ion channels: peptide potassium channel blockers. Explore further ... you need to find out what is known about the molecular diversity of the potassium channel blockers that are part of its venom. ... The Kalium database is a set of information on peptide toxins extracted from scorpion venom that act on potassium channels. ...
Structure of Two New Toxins from the Venom of the Chinese Scorpion Buthus martensi Karsch Blockers of Potassium Channels. (1998 ... Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid ... An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis ... Solution structure of potassium channel inhibiting scorpion toxin Lq2. (1999). Renisio JG, Lu Z, Blanc E, Jin W, Lewis JH, ...
amino acid sequence, animals, elapid venoms, humans, molecular sequence data, neurotoxins, plants, potassium channel blockers, ... Harvey, A L (1997) Recent studies on dendrotoxins and potassium ion channels. General pharmacology, 28 (1). pp. 7-12. ISSN 0306 ... They block some subtypes of voltage-dependent potassium channels in neurons. Dendrotoxins contain 57-60 amino acid residues ... Dendrotoxins act mainly on neuronal K+ channels. Studies with cloned K+ channels indicate that alpha-dendrotoxin from green ...
A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus ... Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid ... An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis ... Scorpion Venoms as a Platform for Drug Development en: Guccione,S. Venoms to Drugs: Venom as a Source for the Development of ...
A NATURAL SCORPION TOXIN WHICH BLOCKS APAMIN-SENSITIVE CALCIUM-ACTIVATED POTASSIUM CHANNELS, 25 STRUCTURES ... Solution structure of BmP02, a new potassium channel blocker from the venom of the Chinese scorpion Buthus martensi Karsch.. Xu ... which had been demonstrated to be a weak blocker of apamin-sensitive calcium-activated potassium channels. Two-dimensional NMR ... which had been demonstrated to be a weak blocker of apamin-sensitive calcium-activated potassium channels. Two-dimensional NMR ...
Novel potassium channel blocker venom peptides from Mesobuthus gibbosus (Scorpiones: Buthidae).. *Elia Diego-García, Steve ...
Dendrotoxin-k is a selective blocker of voltage-gated potassium channels.[35] dendrotoxin-1 inhibits the K+ channels at the pre ... This makes the venom of the the black mamba the most rapid-acting venom of any snake species.[28] The venom consists mainly of ... 1991). "[Potassium channels and epilepsy: evidence that the epileptogenic toxin, dendrotoxin, binds to potassium channel ... a peptide isolated from black mamba venom, is a specific blocker of the L-type calcium channel." Proceedings of the National ...
A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus ... Structure, Molecular Modeling and Function of the First Potassium Channel Blocker, Urotoxin, Isolated from the Venom of the ... MeuTXKbeta1, a scorpion venom-derived two-domain potassium channel toxin-like peptide with cytolytic activity Biochimica et ... Tst26, a novel peptide blocker of Kv1.2 and Kv1.3 channels from the venom of Tityus stigmurus Toxicon, 54, 379-389. ...
... is a selective blocker of large-conductance calcium ion-activated potassium ion channels (BKCa). In single channel recordings, ... Apamin is an 18 amino acid peptide toxin found in bee venom. It is a potent blocker of small conductance Ca2+-activated K+ (SK ... Apamin is used to elucidate the roles of these channels in cells and tissues expressing... ... Iberiotoxin, a peptide purified from venom of the scorpion B. tamulus, ...
I am reading about scorpion venoms and toxins for my bio class and they appear to have a variety of potassium channel blockers ... Do potassium channel blockers affect the resting membrane potential? If they block the resting state "leak" potassium channels ... Potassium channels are necessary for repolarization *Potassium channels participate in controlling the concentration gradient ... But there are many different potassium channels. You may be thinking of blocking the delayed rectifier potassium channel, which ...
This is surprising given the success of some anemone peptides that have been tested, such as the potassium channel blocker from ... channel toxin from Stichodactyla helianthus as potent and selective blockers of the voltage-gated potassium channel Kv1.3. FEBS ... Norton, R.S.; Chandy, K.G. Venom-derived peptide inhibitors of voltage-gated potassium channels. Neuropharmacology 2017, 127, ... 4. Potassium Channel Blockers from Sea Anemones: Therapeutic Leads for the Treatment of Autoimmune Diseases. The voltage-gated ...
They also competed with 125I-apamin (SKca channel blocker) and 125I-kaliotoxin (Kv channel blocker) for binding to rat brain ... voltage-gated potassium channels, as well as on small-conductance calcium-activated potassium channels. It has a unique ... Maurotoxin Kv and SK channels blocker. Maurotoxin is a component of the venom of Scorpio maurus palmatus. Maurotoxin is a ... Product code: N/A. Categories: Kv channels, Potassium channels. Tags: kv, SK. ...
... neurotoxins that act on potassium channels behave as blockers of voltage-sensitive channels, similar to dendrotoxins (DTX) or ... The mixture of cytotoxic and ion channel toxins found in sea anemone venom comprising pore-forming toxins (3,6,25), Na+ channel ... Harvey A, Rowan EG, Vatanpour H, Young LC, Castañeda O, Mebs D, Cerveñansky C & Karlsson E (1996). Potassium channel toxins ... channels. The present data suggest that B. cangicum venom contains at least two bioactive fractions whose activity on cell ...
KW - elapid venoms. KW - molecular models. KW - potassium channel blockers. KW - radioligand assay ... The potassium channel blocker dendrotoxin I was acetylated with acetic anhydride. Mono-acetyl derivatives of all seven lysine ... N2 - The potassium channel blocker dendrotoxin I was acetylated with acetic anhydride. Mono-acetyl derivatives of all seven ... AB - The potassium channel blocker dendrotoxin I was acetylated with acetic anhydride. Mono-acetyl derivatives of all seven ...
Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus Author(s): Marie-France Martin-Eauclaire , ... Antisnake Venom Activity of Hibiscus aethiopicus L. against Echis ocellatus and Naja n. nigricollis Author(s): S. S. Hasson , A ... Ion Channels and Zinc: Mechanisms of Neurotoxicity and Neurodegeneration Author(s): Deborah R. Morris , Cathy W. Levenson. ... Ion Channel-Target Toxicology Author(s): Yonghua Ji , Maria Elena De Lima. Volume: 2012. Year: 2012. ...
2013). BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker. FEBS J. 280: 4839-4852. 23895459 ... channels. BcsTx3, a toxin found in the venom of a Bunodosoma caissarum (from Brazil) has been purified and biochemically and ... 1998). ω-Phonetoxin-IIA: a calcium channel blocker from the spider Phoneutria nigriventer. Pflugers Arch 436: 545-552. 9683727 ... View Proteins belonging to: The Sea Anemone K+ Channel Blocker Toxin, BcsTx3 (BcsTx3) Family ...
  • This short-chain peptide blocks potassium channels, such as Kv1.1, Kv1.2 and Kv1.3. (wikipedia.org)
  • MeuKTX is a potent partial blocker for rat Kv1.1 (rKv1.1), rKv1.2, and human Kv1.3 (hKv1.3). (wikipedia.org)
  • The findings published the week of May 27 in the Proceedings of the National Academy of Sciences reveal that ShK-186 selectively blocks the activity of a protein that promotes inflammation through the Kv1.3 potassium channel. (innovations-report.com)
  • Earlier studies using mice that lack Kv1.3, a potassium channel gene, suggested that Kv1.3 regulated body weight and the basal metabolic rate. (innovations-report.com)
  • These data are quite exciting and strongly support the notion that inhibition of the Kv1.3 channel provides a highly effective method for managing obesity and its associated metabolic abnormalities. (innovations-report.com)
  • While additional studies are needed, the potential clinical relevance of this work is enormous, since a significant number of people are afflicted with obesity and its associated complications, and no Kv1.3 inhibitor, as a drug candidate for obesity, has reached the clinic until now," said Dr. Gary V. Desir, professor of medicine at Yale University, and an expert on the Kv1.3 channel's role in renal potassium secretion and glucose metabolism. (innovations-report.com)
  • Dr. Chandy and his UC Irvine colleague Michael Cahalan discovered Kv1.3 in 1984, and since then they have characterized the role of this channel in immune cells. (innovations-report.com)
  • In the 1990s, Chandy and colleagues found that ShK, a peptide from sun anemone venom, blocks Kv1.3 with high potency. (innovations-report.com)
  • Kaliotoxin2 (KTX2) is a highly selective blocker of voltage-dependent potassium channels Kv1.3 containing 37 amino acid residues. (springermedizin.de)
  • In brain, activation of insulin receptor signaling pathway by insulin induces current suppression and concomitant tyrosine phosphorylation of Kv1.3 channel. (springermedizin.de)
  • The neuroprotective effect of insulin may be due to its crucial role in the regulation of inflammation response and its properties to modulate the activity of Kv1.3 channels in brain. (springermedizin.de)
  • MeuKTX is the orthologue of BmKTX (α-KTx3.6), a known Kv1.3 blocker from the scorpion Mesobuthus martensii, and classified as α-KTx3.13. (epfl.ch)
  • Voltage-gated Kv1.3 and Ca 2+ -dependent KCa3.1 are the most prevalent K + channels expressed by human and rat T cells. (nature.com)
  • However, experiments with Kv1.3 KO rats and Kv1.3 siRNA knockdown or channel-specific inhibition of human T cells show that maximal T-cell responses against autoantigen or repeated tetanus toxoid stimulations require both Kv1.3 and KCa3.1. (nature.com)
  • Electrophysiology studies have implicated the potassium ion (K + ) channel Kv1.3 as having a critical role in the regulation of chronically activated effector memory T (T EM ) cell immune responses. (nature.com)
  • these are the homotetramers of the Shaker-related voltage-gated Kv1.3 ( Kcna3 ) and the Ca 2+ -dependent KCa3.1 K + channels ( Kcnn4 ) 1 . (nature.com)
  • In the context of single cells, channel blockers abrogate Kv1.3 channel function in patch-clamp experiments. (nature.com)
  • This observation raises the possibility that ion channels other than Kv1.3, such as KCa3.1, may have functional activity. (nature.com)
  • It blocks rat Kv1.1, Kv1.2 and Kv1.3 channels expressed in Xenopus oocytes with IC50 values of 13, 16 and 2 nM, respectively. (archives-ouvertes.fr)
  • As previous studies have shown the critical role played by the beta-sheet in Kv1.3 blockers, we suggest that Arg231 is also important for Kv1.3 versus Kv1.2 HTX positive discrimination. (archives-ouvertes.fr)
  • This article gives information on the structure-function relationships of Kv1.2 and Kv1.3 inhibitors targeting developing peptidic inhibitors for the rational design of new toxins targeting given K+ channels with high selectivity. (archives-ouvertes.fr)
  • PAP-1 is a selective inhibitor of Kv1.3, voltage-gated K channel, it potently inhibits human T effector memory cell proliferation with EC50 of 2 nM and delayed hypersensitivity. (csnpharm.com)
  • Selective inhibitor of voltage-gated potassium channels, blocks the Kv1.2/KCNA2 (Kd=1.3 nM) and Kv1.3/KCNA3 (Kd=7.2 nM) channels. (uniprot.org)
  • Method for production of KV1.3 Channel Blockers. (sambomed.co.kr)
  • lymphocytes via Kv1.3 channels. (sambomed.co.kr)
  • Scientists from the Institute of Bioorganic chemistry named after M. M. Shemyakin and Y. A. Ovchinnikov (IBCH RAS) and the University of Leuven in Belgium studied blockers of particular isoforms of the potassium channel (Kv1.3), which is involved in autoimmune processes, and also necessary for the growth of malignant tumors. (buzzon.live)
  • It turned out that, in the polypeptide molecule, it is possible to substitute some amino acids that the blocker lost the ability to communicate with other isoforms of potassium channels, with the exception of selected Kv1.3. (buzzon.live)
  • We knew from experimental research in immunology that the ion channel Kv1.3 is involved in activating immune system responses and that it's linked with chronic inflammation problems in the immune system, such as those you see with multiple sclerosis," says Professor Beech. (healthcanal.com)
  • Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors and cancer cells. (frontiersin.org)
  • In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer. (frontiersin.org)
  • Charybdotoxin (CTX) * and margatoxin (MgTX), which block the predominant voltage-dependent potassium (Kv) channel (Kv1.3) of peripheral lymphocytes, depolarize the plasma membrane ( 3 - 5 ), and thereby inhibit TCR-mediated calcium influx ( 6 - 8 ), IL-2 production ( 9 ), and proliferation ( 9 , 10 ). (rupress.org)
  • an important physiological role of the KCNA3 channel, also known as KV1.3, is to help maintain large electrical gradients for the sustained transport of ions such as Ca2+ that controls T lymphocyte (T cell) proliferation. (diff.org)
  • Thus KV1.3 blockers could be potential immunosuppressants for the treatment of autoimmune disorders (such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis). (diff.org)
  • As a Graduate Student, Christine Beeton was the first to show the benefits of blocking Kv1.1 and Kv1.3 channels with the scorpion venom peptide kaliotoxin to prevent and treat adoptive acute experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. (bcm.edu)
  • She went on showing, in collaboration with Drs. Chandy and Wulff, that encephalitogenic T lymphocytes express more Kv1.3 channels then naïve T lymphocytes do and that targeting Kv1.3 channels only with ShK-Dap22 was sufficient to treat this model of multiple sclerosis. (bcm.edu)
  • As a Postdoctoral Fellow, she continued her collaborative work with Dr. Wulff who showed that terminally differentiated human CCR7- effector memory T (TEM) lymphocytes up-regulate Kv1.3 channels upon activation whereas CCR7+ naïve and central memory T (TCM) lymphocytes up-regulate KCa3.1 channels. (bcm.edu)
  • In collaboration with the groups of Drs. Nepom, Andrews, and Calabresi she showed that T lymphocyte isolated from the synovial fluid of patients with rheumatoid arthritis and from the cerebrospinal fluid of patients with multiple sclerosis express high numbers of Kv1.3 channels. (bcm.edu)
  • Through collaborative work with the groups of Drs. Pennington and Norton, she developed a novel analog of ShK, ShK-186, as a highly potent and selective blocker of Kv1.3 channels. (bcm.edu)
  • Tanner MR, Tajhya RB, Huq R, Gehrmann EJ, Rodarte KE, Atik MA, Norton RS, Pennington MW, Beeton C.. " Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog . (bcm.edu)
  • This subfamily currently exists of six very homologous peptides, originating from scorpion venom: Aa1, AaTX1, AaTX2, AmmTX3, BmTx3 and Discrepin . (wikipedia.org)
  • The pharmaceutical industry has become increasingly interested in biologics from animal venoms as a potential source for therapeutic agents in recent years, with a particularly emphasis on peptides. (rsc.org)
  • To date six drugs derived from venom peptides or proteins have been approved by the FDA, with nine further agents currently being investigated in clinical trials. (rsc.org)
  • This unique book provides an up to date and comprehensive account of the potential of peptides and proteins from animal venoms as possible therapeutics. (rsc.org)
  • In 2006,Professor King founded an agricultural biotechnology company, Vestaron Corporation, that is developing spider-venom peptides discovered in the lab as bioinsecticides.His current research is largely focussed on the development of venom peptides as analgesics for the treatment of chronic pain. (rsc.org)
  • The inhibition of potassium channels by peptides from animal venoms is a subject of broad interest for its physiological and therapeutic applications [ 1 ]. (mdpi.com)
  • Folding profiles of antimicrobial scorpion venom-derived peptides on hydrophobic surfaces: a molecular dynamics study Journal of Biomolecular Structure and Dynamics, 38, 2928-2938. (unam.mx)
  • Novel potassium channel blocker venom peptides from Mesobuthus gibbosus (Scorpiones: Buthidae). (semanticscholar.org)
  • Some peptides were shown to act on the Ca 2+ -activated K + channels (KCa1.1, KCa3.1, KCa2.x. (stackexchange.com)
  • This is surprising given the success of some anemone peptides that have been tested, such as the potassium channel blocker from Stichodactyla helianthus known as ShK. (mdpi.com)
  • In common with many other venomous animals, they produce venom that is a complex mixture of small molecules, peptides and proteins [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. (mdpi.com)
  • 2018). Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel Na1.7. (tcdb.org)
  • Structural determinants of scorpion toxin affinity: the charybdotoxin (alpha-KTX) family of K(+)-channel blocking peptides. (semanticscholar.org)
  • Venom complexity should be further highlighted using combined strategies of large-scale sequencing and data analysis which integrated transcriptomics and proteomics to elucidate new proteins or peptides to be compared among species. (viewpoint.fr)
  • This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools. (ovid.com)
  • A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail , genus Conus . (rug.nl)
  • However, it appears that many of these peptides modulate the activity of ion channels . (rug.nl)
  • Except for the Ca2+ channel specific scorpion toxins, whose threedimensional structure is still unknown, all scorpion toxic peptides have a highly conserved, dense core formed by an α helix and two to three strands of β sheet structural motifs, maintained by disulfide bridges. (diff.org)
  • It blocks voltage-gated potassium channels (K V 1.1/KCNA1, K V 1.2/KCNA2, and K V 1.3/KCNA3) and inhibits apamin-sensitive small conductance calcium-activated channels (SK channels), particularly K Ca 3.1 (IKca1, SK4). (smartox-biotech.com)
  • The venom also inhibits the binding of radiolabeled DTX to synaptosomal membranes (13). (scielo.br)
  • GSK369796 2HCl is an affordable and effective antimalarial and inhibits hERG potassium ion channel repolarization with an IC50 of 7.5 μM. (csnpharm.com)
  • Also inhibits K v 1.3, K v 1.6 and K v 1.1 K + channels (K i values are 4, 37 and 44 pM respectively). (tocris.com)
  • [11] NSAIDs such as ibuprofen , naproxen , or celecoxib inhibits prostaglandin synthesis, leading to reduced production of renin and aldosterone, causing potassium retention. (wikipedia.org)
  • [14] The antibiotic trimethoprim and the antiparasitic drug pentamidine inhibits potassium excretion, which is similar to mechanism of action by amiloride and triamterene. (wikipedia.org)
  • Studies on the interaction of hanatoxin with the Kv2.1 channel show that this tarantula toxin interacts with the S1-S4 domain and inhibits opening by stabilizing a closed state. (rupress.org)
  • Paxilline blocks BK channels in a Ca 2+ -dependent manner, and it potently inhibits BK channels with low free Ca 2+ concentrations ( Sanchez and McManus, 1996 ). (aspetjournals.org)
  • Inhibits voltage-dependent potassium (K + ) channels at nanomolar ranges. (drugfuture.com)
  • δ-conotoxin inhibits fast inactivation of voltage-dependent sodium channels . (rug.nl)
  • κ-conotoxin inhibits potassium channels . (rug.nl)
  • μ-conotoxin inhibits voltage-dependent sodium channels in muscles. (rug.nl)
  • ω-conotoxin inhibits N-type voltage-dependent calcium channels . (rug.nl)
  • The present article's findings suggest that AahG50 may contain a peptidic component active on Kv3.1 channels, which inhibits IKv3.1 in a selective manner. (archives-ouvertes.fr)
  • They block some subtypes of voltage-dependent potassium channels in neurons. (strath.ac.uk)
  • Hence, based on this information I conclude that scorpion venom mainly blocks the repolarization phase of neurons, meaning the maximum firing rate will be drastically reduced because recovery is blocked. (stackexchange.com)
  • Dr. Al-Sabi supervised a team of Ph.D. students and postdocs in normalizing the hypo-excitability of demyelinated neurons using novel and selective potassium channel blockers. (membs.org)
  • We therefore used whole-cell patch-clamp analysis of cockroach dorsal unpaired median (DUM) neurons to study the effects of κ-HXTX-Hv1c on sodium-activated (KNa), delayed-rectifier (KDR) and 'A-type' transient (KA) K+ channels. (ovid.com)
  • Accordingly, we assessed the actions of κ-HXTX-Hv1c on neurotransmitter-gated ion channels in cockroach DUM neurons. (ovid.com)
  • Calcicludine, a venom peptide of the Kunitz-type protease inhibitor family, is a potent blocker of high-threshold Ca2+ channels with a high affinity for L-type channels in cerebellar granule neurons. (pnas.org)
  • HMIMP also potently blocked BK channels in freshly isolated detrusor smooth muscle cells and vagal neurons. (aspetjournals.org)
  • Taken together, these results suggest that associative expression of Kvβ2 subunits with Kv1.1 channels is crucial for developmental acquisition of the unique firing properties of the M-cells among homologous neurons. (zfin.org)
  • These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. (bvsalud.org)
  • Utilizing iberiotoxin-resistance as a footprint for these channels, they have been identified in dentate gyrus granule neurons and in purkinje neurons of the cerebellum. (frontiersin.org)
  • In these neurons, the role of these channels is largely consistent with slow-gated channels that reduce excitability either through an interspike conductance, such as in purkinje neurons, or by replacing fast-gating BK channels that otherwise facilitate high frequency AP firing, such as in dentate gyrus neurons. (frontiersin.org)
  • More recent studies suggest that β4 subunits may also be expressed in some neurons lacking iberiotoxin-resistant BK channels, such as in CA3 hippocampus neurons. (frontiersin.org)
  • While cloned more than 14 years ago, our understanding of the functional role of β4-containing BK potassium channels in neurons is still very limited. (frontiersin.org)
  • Kv2 family "delayed-rectifier" potassium channels are widely expressed in mammalian neurons. (jneurosci.org)
  • Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. (jneurosci.org)
  • In SCG neurons, 100 n m GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. (jneurosci.org)
  • In CA1 neurons, 100 n m GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. (jneurosci.org)
  • In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. (jneurosci.org)
  • In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. (jneurosci.org)
  • The high selectivity of GxTX-1E for Kv2 makes it an attractive tool for studying the function of Kv2 channels in various types of neurons. (jneurosci.org)
  • channels in rat DRG neurons with an IC 50 of 1.1 nM. (sambomed.co.kr)
  • This view is supported by differences in the mode of action of excitatory and depressant toxins on insect neurons, differences in inhibition of their binding by antipeptide antibodies directed against various extracellular sodium channel regions, and the fact that they do not compete reciprocally in binding to fly and lepidoptera neuronal preparations. (diff.org)
  • Rectifier potassium currents in rat DRG neurons were delayed and currents recorded from oocytes expressing K(V)1.2 were suppressed by bis(7)-tacrine, the potency of which was two orders greater than that of tacrine. (epfl.ch)
  • Because potassium channels are the most represented by the superfamily of ion channels, the systematization of the relevant information on the molecules acting on them is an important problem in bioorganic chemistry and pharmacology. (phys.org)
  • In: Morad M, Ebashi S, Trautwein W, Kurachi Y (eds) Molecular physiology and pharmacology of cardiac ion channels and transporters. (springer.com)
  • Cell-Free Expression of Sodium Channel Domains for Pharmacology Studies. (ac.ru)
  • HMIMP, as a highly potent and selective small molecule BK channel blocker, is a very useful tool for examining the pharmacology of BK channels. (aspetjournals.org)
  • Topics covered include chemistry and structural biology of animal venoms, proteomic and transcriptomic approaches to drug discovery, bioassays, high-throughput screens and target identification, and reptile, scorpion, spider and cone snail venoms as a platform for drug development. (rsc.org)
  • Professor Glenn King has been working on animal venoms since 1996.He has extensive experience in the discovery, production, and structural and functional characterization of venom proteins, and is intimately aware of the issues surrounding their development as drugs and insecticides. (rsc.org)
  • Because most animal venoms are acidic, proton-facilitated synergistic action may represent a general strategy for maximizing toxin potency. (sciencemag.org)
  • Most animal venoms contain multiple peptide toxins highly selective for their perspective targets, many of which are ion channels ( 2 , 3 ). (sciencemag.org)
  • Animal venoms are rich in hundreds of toxins with extraordinary biological activities. (bvsalud.org)
  • The molecular mechanism of toxin-induced conformational changes in a potassium channel: relation to C-type inactivation. (springermedizin.de)
  • Imagine that you are studying any particular scorpion, and you need to find out what is known about the molecular diversity of the potassium channel blockers that are part of its venom. (phys.org)
  • In addition, the molecular weight is calculated taking into account the closure of disulfide bonds, and this has an effect on the molecular target (specific isoforms of potassium channels ). (phys.org)
  • Radiolabeled dendrotoxins are useful markers of subtypes of K+ channels in vivo, and structural analogs help to define the molecular recognition properties of different types of K+ channels. (strath.ac.uk)
  • The molecular modeling technique and computed docking indicate the existence of a correlation between the half cystine pairings of the mutated analogs and their activity on the Shaker B K(+) channel. (smartox-biotech.com)
  • The structure of the potassium channel: molecular basis of K+ conduction and selectivity. (semanticscholar.org)
  • He expanded his experience in mutating and studying target channels using whole-cell patch clamp electrophysiological recording and techniques in molecular biology. (membs.org)
  • Our findings should be helpful to develop JZTX-XI into a molecular probe and drug candidate targeting to Kv2.1 potassium channel in the pancreas. (bvsalud.org)
  • Molecular docking analysis indicated that one expressed Zoanthus Kunitz-like peptide, ZoaKuz1, could be a voltage-gated potassium channels blocker and, hence, it was selected for functional studies. (viewpoint.fr)
  • The remarkable molecular diversity of these toxins is borne out by the fact that multiple different toxins can target different components of the same ion channel/receptor. (elifesciences.org)
  • As the "molecular frame" to create a specific blocker was selected as one of the components of Scorpion venom, the molecule of which is a folded chain of several amino acids, or polypeptide capable of clogging potassium channels like a cork. (buzzon.live)
  • Using the method of molecular design, the authors artificially changed the specificity of a component of Scorpion venom so that he began to only block the potassium channels responsible for the development of autoimmune diseases and cancer. (buzzon.live)
  • The biological activity test was conducted on the powder formulation of the chosen plants, Dillenia ovata and Dillenia parviflora at a ratio of 30:70, for anti-inflammatory activity ex vivo on a panel of molecular targets through ion channel inhibition including voltage-gated sodium channel, voltage-gated potassium channel, and the cardiac ion as human ether-a-go-go related gene. (bvsalud.org)
  • To investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms. (bvsalud.org)
  • Family of low molecular weight (~7K) proteins isolated from the venom of mamba snakes. (drugfuture.com)
  • The molecular basis for type II BK channels was revealed in 1999 when random cDNA sequences began flooding DNA databases and perusing BKologists identified three additional accessory subunit family members (β2, β3, and β4) similar to the previously cloned β1 that modulate the BK pore-forming α subunit. (frontiersin.org)
  • Here, BmKKx2, the first specific blocker of hERG channel derived from scorpion Mesobuthus martensii , was identified and the turret role of hERG channel was re-investigated using BmKKx2 as a molecular probe. (biomedcentral.com)
  • In recent years, other structural features of channel turrets were also revealed by the specific scorpion toxins as the molecular probes. (biomedcentral.com)
  • Using the scorpion toxin BeKm-1 as a molecular probe, different conformational states in the turret of hERG channel have been reported. (biomedcentral.com)
  • This high-affinity blockade depends on the expression of dipeptidyl peptidase-like proteins (DPP) DPP6 and DPP10 , which are proteins that co-assemble with the alpha-subunits of Kv4 channels. (wikipedia.org)
  • Once they enter the body, they selectively act on certain ion channels - membrane proteins that play a leading role in the transmission of signals in the nervous system. (phys.org)
  • Dendrotoxins are small proteins isolated from mamba (Dendroaspis) snake venoms. (strath.ac.uk)
  • Variation of cytochrome oxidase-I gene and venom proteins of Rhopalurus junceus populations in the Moanicum sector: Pharmacological implications Journal of Pharmacy and Pharmacognosy Research, 9, 1-12. (unam.mx)
  • K + channels are tetrameric membrane proteins that selectively conduct K + across cellular membranes. (nature.com)
  • Assist the expectant parents to confuse vomiting, which is excreted in the late 1820s, farmers had few options for contraception (see good sexual relationships during our daily attempts to produce an antidysrhythmic in ca toxicity and is a cause of these venom proteins are being formed through the production of hydrochloric acid. (alsrideforlife.org)
  • It represents only 0.1% of the venom proteins, and displaces [125 I]alpha-dendrotoxin from its site on rat brain synaptosomes with an IC50 value of 16 nm. (archives-ouvertes.fr)
  • Ion channels are proteins and, as their name suggests, they allow ions-usually sodium, potassium, or calcium ions-to move in and out of cells. (elifesciences.org)
  • For most ion channel proteins, the ion conduction pathway is not always open, but is dynamically regulated so that the pore opens and closes in response to a particular stimulus ( Hille, 2001 ). (rupress.org)
  • those proteins are "the bit that will kill you," he says.Seymour says he has unpublished evidence that Yanagihara's technique for collecting venom deactivates the heart toxins along with other components. (zsxingying.com)
  • Porins should be tested on heart cells and tissues, he says, to find out whether they directly affect the heart.Yanagihara acknowledges that jellyfish venom contains other toxins, including molecules that break down lipids and proteins, but her studies convinced her that porins are the main and fastest killer. (zsxingying.com)
  • Iberiotoxin, a peptide purified from venom of the scorpion B. tamulus, is a selective blocker of large-conductance calcium ion-activated potassium ion channels (BKCa). (biomol.com)
  • It is a potent blocker of small conductance Ca2+-activated K+ (SK, KCa2) channels that is more effective at SK2 than SK1 and SK3 (IC50 values are 0.06-0.4, 1-12, and 1-13 nM, respectively). (biomol.com)
  • The resting membrane potential is largely set by the electrical conductance through those channels. (stackexchange.com)
  • Probably not, since though the cell would be losing less potassium through this conductance, what matters more to the concentration gradient of potassium are the sodium/potassium pumps. (stackexchange.com)
  • NS19504 is a selective activator of large-conductance Ca2+-activated potassium channels (BKCa, KCa1.1) with EC50 of 11 μM. (csnpharm.com)
  • The prototypic κ-HXTX-Hv1c selectively blocks native and expressed cockroach large-conductance calcium-activated potassium (BKCa or KCa1.1) channels, but not their mammalian orthologs. (ovid.com)
  • In contrast to what is observed in the Kv2.1 channel, we find that hanatoxin shifts the conductance-voltage relation to negative voltages, making it easier to open the channel with membrane depolarization. (rupress.org)
  • Although these actions of the toxin are subtle in the wild-type channel, strengthening the toxin-channel interaction with mutations in the S3b helix of the S1-S4 domain enhances toxin affinity and causes large shifts in the conductance-voltage relationship. (rupress.org)
  • The large-conductance voltage-gated and calcium-dependent K + (BK) channels are widely distributed and play important physiological roles. (aspetjournals.org)
  • 0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. (bvsalud.org)
  • Small conductance calcium-activated potassium channels link elevations of intracellular calcium ions to membrane potential, exerting a hyperpolarizing influence when activated. (elsevier.com)
  • Single channel recordings for heterodimeric and double mutant constructs in which ion conduction is rescued suggest that the V478W mutation does not dramatically alter unitary conductance. (rupress.org)
  • While most large-conductance, calcium-, and voltage-activated potassium channels (BK or Maxi-K type) are blocked by the scorpion venom iberiotoxin, the so-called "type II" subtype has the property of toxin resistance. (frontiersin.org)
  • SK channels ( S mall conductance calcium-activated K (potassium) channels ) are a subfamily of Ca 2+ -activated K + channels . (thefullwiki.org)
  • The intracerebroventricular administration of tetraethylammonium (TEA, a nonspecific blocker of K(+) channels), glibenclamide (an ATP-sensitive K(+) channel blocker), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel blocker) or apamin (a small-conductance calcium-activated K(+) channel blocker) combined with a subeffective dose of hesperidin (0.01 mg/kg, intraperitoneally [i.p.]) was able to produce a synergistic antidepressant-like effect in the mice TST. (sigmaaldrich.com)
  • Single channel conductance was not affected by the different glycosylation states of Kv1.2. (epfl.ch)
  • Studies with cloned K+ channels indicate that alpha-dendrotoxin from green mamba Dendroaspis angusticeps blocks Kv1.1 and Kv1.2 channels in the nanomolar range. (strath.ac.uk)
  • Does not inhibit the potassium channels Kv1.1/KCNA1, Kv1.4/KCNA4, Kv1.5/KCNA5, Kv2.1/KCNB1, Kv11.1/KCNH2, KCa3.1/KCNN4, KCa1.1/KCNMA1 and the sodium channel Nav1.5/SCN5A. (uniprot.org)
  • Purification, characterization, and precursor nucleotide sequence of KTX2 from Androctonus australis venom. (springermedizin.de)
  • For decades, the study of venomous animals has focused on the isolation and biochemical characterization of specific venom components that have medical or biotechnological importance. (springer.com)
  • Dhawan RD, Joseph S, Sethi A, Lala AK (2002) Purification and characterization of a short insect toxin from the venom of the scorpion Buthus tamulus . (springer.com)
  • Functional, proteomic and transcriptomic characterization of the venom from Micrurus browni browni: Identification of the first lethal multimeric neurotoxin in coral snake venom Journal of Proteomics, 225, 103863. (unam.mx)
  • Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico Toxicon, 184, 10-18. (unam.mx)
  • Biochemical characterization revealed that BcsTx3 is a 50 amino acid peptide crosslinked by four disulfide bridges, and sequence comparison allowed BcsTx3 to be classified as a novel type of sea anemone toxin acting on K V channels. (tcdb.org)
  • Here, we report the purification, sequencing and functional characterization of a new K(+) channel blocker (MeuKTX) from the venom of the scorpion Mesobuthus eupeus. (epfl.ch)
  • Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. (semanticscholar.org)
  • Garcia et al (1994) Purification and characterization of three inhibitors of voltage-dependent K + channels from Leiurus quinquestriatus var. (tocris.com)
  • We developed a Venomics approach combining transcriptomic and proteomic characterization of 191 species and identified 20,206 venom toxin sequences. (bvsalud.org)
  • Abe, T., Alema, S. and Miledi, R. (1977) Isolation and characterization of presynaptically acting neuro Toxins from the venom of Bungarus snakes. (springer.com)
  • Besides above progress of structure and function relationships of different potassium channel turrets, characterization of more potassium channel extracellular pore entryways remains a challenge nowadays due to the difficulties in determining the crystal structures of additional potassium channels. (biomedcentral.com)
  • This is particularly important for venomous species, such as scorpions, since they are relevant not only for their biology or ecology but mostly for the venom they produce, which is restricted to a specific organ: the venom gland. (springer.com)
  • From Song Dynasty in ancient China, scorpions and their venoms have been applied in traditional medicine for treating neurological disorders, such as pain, stroke, and epilepsy. (intechopen.com)
  • The deadly toxins produced by many creatures, including spiders, snakes, and scorpions, work by blocking the ion channels that are essential for the normal operation of many different types of cells. (elifesciences.org)
  • Animals such as scorpions have venoms that block potassium and other ion channels. (medindia.net)
  • We investigated the in-vitro process of cell death caused by two Iranian scorpions Odontobuthus doriae and Bothutus salceyi venom on human cell lines. (ac.ir)
  • Most of the scorpion toxins have been isolated from the venoms of scorpions in the family Buthidae. (ac.ir)
  • Venoms from marine and terrestrial animals (cone snails, scorpions, spiders, snakes, centipedes, cnidarian, etc.) can be seen as an untapped cocktail of biologically active compounds, being increasingly recognized as a new emerging source of peptide-based therapeutics. (readbyqxmd.com)
  • Bearg, W.J. (1961) Scorpions biology and effect of the venom. (springer.com)
  • Na+ channel specific toxins from scorpions are modifiers of the channel gating mechanism, and were initially divided into two groups: α and β toxins. (diff.org)
  • Dequalinium Chloride is a PKC inhibitor with IC50 of 7-18 M, and also a selective blocker of apamin-sensitive K channels with IC50 of 1.1 M. (csnpharm.com)
  • Agitoxin-2 is a potent and selective blocker of the Shaker type voltage-gated K v 1.3 and K v 1.1 channels. (sambomed.co.kr)
  • We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). (jneurosci.org)
  • MeuKTX (α-KTx 3.13), which belongs to the α-KTx toxin subfamily, is a neurotoxin present in the venom of Mesobuthus eupeus. (wikipedia.org)
  • MeuKTX is a neurotoxin found in the venom of the scorpion Mesobuthus eupeus which belongs to the family Buthidae. (wikipedia.org)
  • Role of G-protein coupled pathways in modulating the cardiotoxic effects produced by Indian red scorpion ( Mesobuthus tamulus ) venom were examined. (springer.com)
  • Deshpande SB, Alex AB, Jagannadham MV, Rao GRK, Tiwari AK (2005) Identification of a novel pulmonary oedema producing toxin from the Indian red scorpion ( Mesobuthus tamulus) venom. (springer.com)
  • The basis was taken the poison motley Scorpion Mesobuthus eupeus, can block potassium channels "gateway" for potassium ions across the cell membrane. (buzzon.live)
  • BmP02 is a 28-amino acid residue peptide purified from the venom of the Chinese scorpion Buthus martensi Karsch, which had been demonstrated to be a weak blocker of apamin-sensitive calcium-activated potassium channels. (rcsb.org)
  • Commonly used BK channel inhibitors are peptide toxins that are isolated from scorpion venoms. (aspetjournals.org)
  • Potassium channels regulate cell membrane potential and control a variety of cellular processes. (innovations-report.com)
  • In single channel recordings, iberiotoxin can reversibly block outward currents mediated by BKCa in excised membrane patches from bovine aortic smooth muscle with an IC50 value of 250 pM. (biomol.com)
  • Do potassium channel blockers affect the resting membrane potential? (stackexchange.com)
  • I would rephrase this to "Sodium/potassium pumps establish the concentration gradients of sodium and potassium across the cell membrane. (stackexchange.com)
  • You may be thinking of blocking the delayed rectifier potassium channel, which shouldn't do much at all to change the resting membrane potential. (stackexchange.com)
  • hence, scorpion venom will not affect the resting membrane potential too much. (stackexchange.com)
  • Voltage-dependent potassium channels (K v s) gate in response to changes in electrical membrane potential by coupling a voltage-sensing module with a K + -selective pore. (pnas.org)
  • Neurotoxins purified from Chinese scorpion Buthus Martensii Karsch (BmK) are considered as the main active ingredients, which act on membrane ion channels. (intechopen.com)
  • Recent advances underlying medical studies have illuminated that several neurological disorders such as epilepsy, chronic pain, multiple sclerosis, stroke, brain tumor etc. are induced by dysfunction of membrane ion channels [ 1 , 2 , 3 ]. (intechopen.com)
  • Diazoxide is an ATP-sensitive potassium channel activator which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions. (csnpharm.com)
  • Voltage-activated ion channels open and close in response to changes in membrane voltage, a property that is fundamental to the roles of these channels in electrical signaling. (rupress.org)
  • Next, the researchers received the modified polypeptide in the system of synthesis based on E. coli and have studied its ability to block potassium current through the membrane. (buzzon.live)
  • The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. (bvsalud.org)
  • we found that mutation of V478 to W results in a channel that cannot conduct ions even though the voltage sensors are competent to translocate gating charge in response to membrane depolarization. (rupress.org)
  • In voltage-gated potassium (K v ) channels, a K + selective pore opens and closes in response to changes in membrane voltage ( Yellen, 1998 ). (rupress.org)
  • B) Membrane folding diagram for a K v channel showing six TM domains. (rupress.org)
  • Normally these seven segments cluster in a tight clump, forming one of four sides of a narrow channel through the membrane ( as shown below left ). (myhosting.com)
  • Embedded nearby in the same outer membrane of the nerve ending are the ion channels which open when the cyclic AMP or cyclic GDP chemically bind onto each subunit. (myhosting.com)
  • The toxin works by inhibiting the activity of a specific potassium ion channel - a pore in the cell membrane that opens and closes in response to electrical signals and indirectly enhances delivery of a intracellular messenger, the calcium ion. (healthcanal.com)
  • [ 1 ] SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium. (thefullwiki.org)
  • A loop between the fifth and sixth trans membrane domain forms the potassium ion selectivity filter . (thefullwiki.org)
  • Voltage-dependent K + channels (Kv), a superfamily comprised of 12 subfamilies (Kv1-Kv12), play a key role in the maintenance of resting membrane potential and the control of action potentials ( Hille, 2001 ). (frontiersin.org)
  • Kv channels also control leukocyte membrane potential and play a role in immune system responses ( Cahalan and Chandy, 2009 ). (frontiersin.org)
  • Interestingly, Kv channels in anergized lymphocytes actively suppress IL-4 production, and these functions are consistent with a role in regulating the membrane potential and calcium signaling. (rupress.org)
  • One important intrinsic determinant of T cell responsiveness is the membrane potassium permeability, which is modulated by potassium channels. (rupress.org)
  • Given the well established role for Kv channels in regulating cell volume, apoptosis, membrane potential, and calcium influx, and the critical role of calcium in T cell differentiation, and IL-2 production in particular, we hypothesized that Kv channels may contribute to the unique physiology and responsiveness of naive and differentiated T cells. (rupress.org)
  • On the other hand, β type toxins bind to site 4 independently of membrane potential and affect sodium channel activation. (diff.org)
  • A protein complex that forms a transmembrane channel through which potassium ions may cross a cell membrane in response to changes in membrane potential. (epfl.ch)
  • Chen H, Heinemann SH (2001) Interaction of scorpion alpha-toxin with cardiac sodium channels: binding properties and enhancement of slow inactivation. (springer.com)
  • Maurotoxin is a 34-residue toxin isolated from the venom of the Tunisian chactoid scorpion Scorpio maurus palmatus and contains four disulfide bridges that are normally found in long-chain toxins of 60-70 amino acid residues, which affect voltage-gated sodium channels. (smartox-biotech.com)
  • Sea anemone neurotoxins that affect sodium channels slow down the inactivation phase of the currents without affecting the activation process, so that the channels remain open for a longer period of time leading to a prolongation of the action potential duration (1,3). (scielo.br)
  • There, he studied the biophysical and pharmacological characteristics of voltage-gated sodium channels from human, rats and bacteria. (membs.org)
  • Long-chain toxins of BmK, composed of 58-76 amino acids, could specifically recognize voltage-gated sodium channels (VGSCs). (intechopen.com)
  • both the drugs block epithelial sodium channels in the collecting tubules, thereby preventing potassium excretion into urine. (wikipedia.org)
  • Scorpion toxins specific for insect voltage-gated sodium channels (Navs) have been considered as one of the most promising insecticide alternatives due to their host specificity, rapidly evoked toxicity, biodegradability and the lack of resistance. (bvsalud.org)
  • The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. (rug.nl)
  • [17] Mu-conotoxins target the muscle-specific voltage-gated sodium channels, [7] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues. (rug.nl)
  • Voltage-gated Sodium Channels Isolated from the Chinese Bird Spider Ornithoctonus hainana. (sambomed.co.kr)
  • Scorpion toxins have been divided into two principal types (α and β), based on their pharmacological effects on sodium channels, as verified by means of electrophysiological measurements and by their binding characteristics. (diff.org)
  • The receptor sites of scorpion α and ß toxins on insect sodium channels interact allosterically. (diff.org)
  • Using binding studies, it was demonstrated for the first time positive allosteric interactions between receptor sites 3 and 4 on insect sodium channels, which explain in part the synergic effects observed between α- and ß-toxins in vivo. (diff.org)
  • A-type potassium currents can be generated by Kv1.4 , Kv3.3 , Kv3.4 , all members of Kv4 and Erg3 channels. (wikipedia.org)
  • The influence of AmmTX3 on the overall A-type potassium currents hence depends on the specific channel types that mediate this current in the cell. (wikipedia.org)
  • The effectiveness of MeuKTX as a blocker for these potassium channels is summarized below: Complete inhibition of ionic currents was observed at higher concentrations (2 μM) for all three potassium channels. (wikipedia.org)
  • At the single channel level, the toxin does not modify the unitary current amplitude, but decreases ensemble currents by increasing the number of depolarizing epochs that failed to elicit any opening. (smartox-biotech.com)
  • In crayfish muscle fibers, Bunodosoma cangicum whole venom selectively blocks the I K(Ca) currents. (scielo.br)
  • Its venom selectively blocks the Ca 2+ -dependent K + current (I K(Ca) ) present in crayfish muscle fibers in a reversible manner without affecting voltage-gated Ca 2+ or K + currents (15). (scielo.br)
  • Furthermore, the venom reduces I K(Ca) in chromaffin cells without modifying voltage-gated Na + , Ca 2+ or K + currents (15). (scielo.br)
  • Kv2.1 channel currents in pancreatic beta-cells are thought to contribute to action potential repolarization and thereby modulate insulin secretion. (bvsalud.org)
  • Two-microelectrode voltage clamp experiments had showed that the toxin inhibited Kv2.1 potassium currents expressed in Xenopus Laevis oocytes. (bvsalud.org)
  • Under the whole-cell patch-clamp mode, JZTX-XI could completely inhibit hKv2.1 and hNav1.5 channels currents expressed in HEK293T cells with IC50 values of 95.8 nmol/L and 437.1 nmol/L respectively. (bvsalud.org)
  • The mutant R3A-JZTX-XI could also inhibit hKv2.1 and hNav1.5 channel currents expressed in HEK293T cells with IC50 values of 1.22 micromol/L and 1.96 micromol/L respectively. (bvsalud.org)
  • IK1 inhibitor PA-6 (PA-6), a pentamidine analogue, is a selective and potent IK1 (KIR2.x ion-channel-carried inward rectifier current) inhibitor, with IC50 values of 12-15 nM for human and mouse KIR2.x currents. (csnpharm.com)
  • 1 μM κ-HXTX-Hv1c failed to significantly inhibit cockroach KNa and KDR channels, but did cause a 30 ± 7% saturating inhibition of KA channel currents, possibly via a Kv4 (Shal-like) action. (ovid.com)
  • Third, zKv1.1a expressed in Xenopus oocytes functioned as low-threshold K + channels, and its currents were enhanced by coexpression of zKvβ2b subunits. (zfin.org)
  • Kv2 channels produce "delayed-rectifier" currents that activate more slowly than many other voltage-dependent potassium channels, including most Kv1, Kv3, and Kv4 family channels. (jneurosci.org)
  • Head-to-Tail Cyclization after Interaction with Trypsin: A Scorpion Venom Peptide that Resembles Plant Cyclotides Journal of Medicinal Chemistry, 63, 9500-9511. (unam.mx)
  • Targeting KCa1.1 channels with a scorpion venom peptide for the therapy of rat models of rheumatoid arthritis. (medindia.net)
  • The results obtained with ShK-186 are consistent with what one would expect to see with a potent inhibitor of this channel. (innovations-report.com)
  • The venom-induced decrease in rate and increase in force were sensitive to atropine, N -ω-nitro- l -arginine methylester (NO synthase inhibitor) and methylene blue (guanylyl cyclase inhibitor). (springer.com)
  • Revealing the architecture of a K+ channel pore through mutant cycles with a peptide inhibitor. (semanticscholar.org)
  • For example, charybdotoxin blocks voltage-gated Kv channels with exquisite potency [Ki (inhibitor constant) in the subnanomolar range] ( 4 ), causing uncontrollable hyperexcitability of the nervous system ( 5 , 6 ). (sciencemag.org)
  • TAK-438, a potassium proton pump inhibitor, can reversibly inhibit HK ATPase with IC50 of 17 nM and does not affect NaK ATPase. (csnpharm.com)
  • JZTX-XII shares 80% sequence identity with phrixotoxin1, a potent inhibitor for Kv4.2 and Kv4.3 channels. (unboundmedicine.com)
  • ACE inhibitors , angiotensin receptor blockers , [11] and calcineurin inhibitor immunosuppressants such as ciclosporin and tacrolimus . (wikipedia.org)
  • It is structurally homologous to the Kunitz-type protease inhibitor, to dendrotoxins, which block K+ channels, and to the protease inhibitor domain of the amyloid beta protein that accumulates in Alzheimer disease. (pnas.org)
  • Chimeras in which S3b-S4 paddle motifs are transferred between Kv2.1 and Shaker Kv channels, as well as experiments with the related tarantula toxin GxTx-1E, lead us to conclude that the actions of tarantula toxins are not simply a product of where they bind to the channel, but that fine structural details of the toxin-channel interface determine whether a toxin is an inhibitor or opener. (rupress.org)
  • BmKKx2 was found to block hERG channel with an IC 50 of 6.7 ± 1.7 nM and share similar functional surface with the known hERG channel inhibitor BeKm-1. (biomedcentral.com)
  • Their venoms are cocktails of bioactive molecules, called toxins, which are responsible for their toxicity. (intechopen.com)
  • What is the underlying cause of toxicity of these venoms? (elifesciences.org)
  • Scorpion venom toxicity is of major concern due to its influence on human activities and public health. (ac.ir)
  • Pore-blocking toxins inhibit voltage-dependent K + channels (K v channels) by plugging the ion-conduction pathway. (elifesciences.org)
  • VU590 dihydrochloride has been reported to inhibit the renal, outer medullary potassium channel (KIR1.1) with IC50 of 294 nM, and also able to inhibit the inward rectifying potassium channel KIR7.1. (csnpharm.com)
  • Since our own studies had identified Kv1.3's presence in injured blood vessels, which are also often complicated by chronic inflammation, we wanted to see if the same immune system blockers would inhibit neointimal hyperplasia. (healthcanal.com)
  • A cream containing copper gluconate is then applied to inhibit the injected venom. (zsxingying.com)
  • Dendrotoxins act mainly on neuronal K+ channels. (strath.ac.uk)
  • Scorpion venom mostly affects neuronal firing activity by inhibiting recovery. (stackexchange.com)
  • Then CaC, in the nanomolar range, appears to be a highly potent blocker of an L-subtype of neuronal Ca2+ channels. (pnas.org)
  • Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. (jneurosci.org)
  • Results showed that the antidepressant-like effect of hesperidin in TST may involve, at least in part, the modulation of neuronal excitability through inhibition of K(+) channels and may act through a mechanism dependent on the inhibition of L-arginine-NO pathway. (sigmaaldrich.com)
  • Amino acid residues of MTX that were studied for Shaker B recognition were selected on the basis of their homologous position in charybdotoxin, a three disulfide-bridged scorpion toxin also active on this channel type. (smartox-biotech.com)
  • We have solved the crystal structure of paddle chimera, a K v channel in complex with charybdotoxin (CTX), a pore-blocking toxin. (elifesciences.org)
  • have used x-ray crystallography to study the structure of the complex that is formed when charybdotoxin (CTX), a toxin that is found in scorpion venom, blocks a voltage-gated potassium channel. (elifesciences.org)
  • Despite this potent and selective action on insect KCa1.1 channels, we found that the classical KCa1.1 blockers paxilline, charybdotoxin and iberiotoxin, which all block insect KCa1.1 channels, are not lethal in crickets. (ovid.com)
  • In general, the M. eupeus scorpion venom has a lethal dose (LD50) of 4.5 (IV), 8.75 (IP), and 11.5 mg/kg (SC). (wikipedia.org)
  • Potassium voltage-gated channel subfamily A member 2 also known as Kv1.2 is a protein that in humans is encoded by the KCNA2 gene. (epfl.ch)
  • Here, we tested chimaeras of rat Kv1.2 with the hERG channel for function in Xenopus oocytes and for overexpression in Pichia. (epfl.ch)
  • Sea anemones contain a variety of biologically active substances including polypeptide toxins which affect sodium and potassium channels (1,2). (scielo.br)
  • 2010). Novel class of spider toxin: active principle from the yellow sac spider Cheiracanthium punctorium venom is a unique two-domain polypeptide. (tcdb.org)
  • The toxic arsenals of venomous organisms contain polypeptide toxins that block ion channels to enable the rapid paralysis of a potential prey or foe. (pnas.org)
  • Jingzhaotoxin-XII (JZTX-XII), a 29-residue polypeptide, was purified from the venom of the Chinese tarantula Chilobrachys jingzhao. (unboundmedicine.com)
  • Calcicludine (CaC) is a 60-amino acid polypeptide from the venom of Dendroaspis angusticeps. (pnas.org)
  • Employees at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences (IBCh RAS) have created Kalium , a database for peptide toxins from scorpion venom. (phys.org)
  • The Kalium database is a set of information on peptide toxins extracted from scorpion venom that act on potassium channels. (phys.org)
  • Sea anemone venoms are a rich source of peptide toxins which provide tools for studying the structures and functions of ion channels. (tcdb.org)
  • are peptide toxins that are isolated from various scorpion venoms. (aspetjournals.org)
  • Peptide toxins with different pharmacological properties are widely used to study BK channels. (aspetjournals.org)
  • GAL-021 a new intravenous Potassium Channel KCa1.1 blocker. (csnpharm.com)
  • the Ca 2+ -activated K + channels are activated when Ca 2+ enters the cell, which is an event typically associated with action potentials too. (stackexchange.com)
  • Also, tetrodotoxin could not block the action potentials in a Bcg-3-pretreated preparation, suggesting a possible interaction of Bcg-3 with Na + channels. (scielo.br)
  • HMIMP did not change the action potentials of ventricular myocytes, confirming its lack of effect on cardiac ion channels. (aspetjournals.org)
  • Studies have shown that β4 dramatically promotes BK channel opening by shifting voltage sensor activation to more negative voltage ranges, but also slows activation to timescales that theoretically preclude BK ability to shape action potentials (APs). (frontiersin.org)
  • 2013). BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker. (tcdb.org)
  • Comparison of sea anemone and scorpion toxins binding to Kv1 channels: an example of convergent evolution. (semanticscholar.org)
  • A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties. (semanticscholar.org)
  • Midazolam can block hERG K+ channel and cause the speed of inactivation faster. (bvsalud.org)
  • We began by examining whether the intracellular gate moves using probes that interact with the intracellular pore and by studying the inactivation properties of heterodimeric channels that are competent to conduct ions. (rupress.org)
  • steady- state Na + channel inactivation. (sambomed.co.kr)
  • Scorpion α toxins bind to site 3 of the Na+ channels in a voltage dependent mode, slowing or blocking the inactivation mechanism of these channels. (diff.org)
  • At this concentration, MeuKTX also affects rKv1.6 and shaker IR channels. (wikipedia.org)
  • Of this host of toxins, the majority were tested on Shaker-related channels (subfamily KV1.x). (stackexchange.com)
  • Here, using MTX and/or MTX(Pi1) as models, we investigated how the type of folding influences toxin recognition of the Shaker B potassium channel. (smartox-biotech.com)
  • Our data indicate clearly that Lys(23) and Tyr(32) (two out of ten amino acid residues studied) are the most important residues for Shaker B channel blockage by MTX. (smartox-biotech.com)
  • Here, we analyzed the effects of synthetic maurotoxin on voltage-gated Shaker potassium channels (ShB) expressed in Xenopus oocytes. (smartox-biotech.com)
  • hERG and Shaker IR) and three cloned voltage-gated sodium channel isoforms (Na(V)1.2, Na(V)1.4 and BgNa(V)1.1), all expressed in Xenopus laevis oocytes. (tcdb.org)
  • BcsTx3 showed a high affinity for Drosophila Shaker IR channels over rKv1.2, hKv1.3 and rKv1.6, and was not active on Na V channels. (tcdb.org)
  • Potent Shaker K + channel blocker (K i = 0.64 nM). (tocris.com)
  • Gross et al (1996) Agitoxin footprinting the shaker potassium channel pore. (tocris.com)
  • Here we investigated the interaction of hanatoxin with the Shaker Kv channel, a voltage-activated channel that has been extensively studied with biophysical approaches. (rupress.org)
  • Using a range of previously characterized mutants of the Shaker Kv channel, we find that hanatoxin stabilizes an activated conformation of the voltage sensors, in addition to promoting opening through an effect on the final opening transition. (rupress.org)
  • SK potassium channels share the same basic architecture with shaker-like voltage-gated potassium channels . (thefullwiki.org)
  • Venom components of the scorpion Centruroides limpidus modulate cytokine expression by T helper lymphocytes: Identification of ion channel-related toxins by mass spectrometry International Immunopharmacology, 84, 106505. (unam.mx)
  • Short-chain BmK toxins, containing 28-40 amino acids, are found to modulate the potassium or chloride channels. (intechopen.com)
  • 2012). A venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei exhibits cytolytic activities. (tcdb.org)
  • Jingzhaotoxin-XI (JZTX-XI) is a novel peptide neurotoxin isolated from the venom of the spider Chilobrachys jingzhao. (bvsalud.org)
  • Babin, D.R., Watt, D.D., Goos, S.M. and Mlejnek, R.V. (1974) Amino acid sequences of neurotoxin protein variants from the venom of Centruroides sculpturatus Ewing. (springer.com)
  • All SK channels can be pharmacologically blocked by quaternary ammonium salts of a plant-derived neurotoxin bicuculline . (thefullwiki.org)
  • Together, these results show that CTX binds to a K + channel in a lock and key manner and interacts directly with conducting ions inside the selectivity filter. (elifesciences.org)
  • The potassium ion channel is made up of four subunits, and the pore contains four ion-binding sites that form a 'selectivity filter': it is this filter that ensures that only potassium ions can pass through the channel when it is open. (elifesciences.org)
  • A high-affinity, nonpeptide, synthesized BK channel blocker with selectivity against other ion channels has not been reported. (aspetjournals.org)
  • High-affinity, synthesized small molecule BK channel blockers with good ion channel selectivity remain to be identified. (aspetjournals.org)
  • A long-standing problem in studying the function of Kv2 channels is a lack of a high-selectivity blocker. (jneurosci.org)
  • [1] A number of medications can also cause high blood potassium including spironolactone , NSAIDs , and angiotensin converting enzyme inhibitors . (wikipedia.org)
  • The venom is usually fast-acting, and it is composed by a mixture of neurotoxines, enzyme inhibitors, etc. (diff.org)
  • Hemitoxin, the first potassium channel toxin from the venom of the Iranian scorpion Hemiscorpius lepturus. (archives-ouvertes.fr)
  • Typically, α-KTxs affect voltage-gated potassium channels. (wikipedia.org)
  • Therefore, Lys 5 is probably part of the functional site for dendrotoxin's binding to the voltage-dependent K+ channels. (strath.ac.uk)
  • In contrast, neurotoxins that act on potassium channels behave as blockers of voltage-sensitive channels, similar to dendrotoxins (DTX) or to mast cell degranulating peptide isolated from mamba snakes (12,13) and bee venoms (14), respectively. (scielo.br)
  • Effects of MeuKTX on ten cloned potassium channels in Xenopus oocytes were evaluated using two-electrode voltage-clamp recordings. (epfl.ch)
  • Here, we describe a peptide isolated from a cone snail that blocks voltage-gated potassium channels by disrupting the intramolecular hydrogen bond network that governs the dynamic distribution of these structural water molecules. (pnas.org)
  • Animal toxins targeting K v s are classified as pore blockers, which physically plug the ion conduction pathway, or as gating modifiers, which disrupt voltage sensor movements. (pnas.org)
  • however, the reported minimum concentrations for activating TRPV1 channel or inhibiting voltage-gated potassium (Kv) channels (both in the micromolar range) appear too high to be biologically relevant. (sciencemag.org)
  • Peptide 401 is a blocker of voltage-sensitive K + channels with convulsant activity. (csnpharm.com)
  • Voltage-clamp experiments on a variety of excitable cells have shown that CaC specifically blocks most of the high-threshold Ca2+ channels (L-, N-, or P-type) in the 10-100 nM range. (pnas.org)
  • Protein toxins from venomous organisms commonly target the S1-S4 voltage-sensing domains in these channels and modify their gating properties. (rupress.org)
  • Voltage-activated ion channels play a wide range of critical roles in electrical and chemical signaling within biological systems. (rupress.org)
  • In tetrameric Kv channels, each of the four subunits contain six transmembrane helices (S1-S6), with the S5-S6 forming the centrally located pore domain, and the S1-S4 helices forming each of four voltage-sensing domains. (rupress.org)
  • In Nav and Cav channels, the four voltage-sensing domains are contained within a single α subunit, such that the four voltage-sensing domains are not identical ( Catterall, 2012 ). (rupress.org)
  • The inhibitory effect of HMIMP was not voltage-dependent, nor did it require opening of BK channels. (aspetjournals.org)
  • HMIMP had no effect on human Na V 1.5 (1 μM), Ca V 3.2, L-type Ca 2+ , human ether-a-go-go-related gene potassium channel, KCNQ1+minK, transient outward K + or voltage-dependent K + channels (100 nM). (aspetjournals.org)
  • Each neuron possesses a unique firing property, which is largely attributed to heterogeneity in the composition of voltage-gated ion channel complexes. (zfin.org)
  • Out of the Dillenia formulation which contained various compounds, oleamide showed the highest percentages of inhibition at 8.0-20.0%, and 6.2-14.2% in voltage-gated sodium channel, and voltage-gated potassium channel which had slightly lower values than the oleamide standard, and no effect as 0.0% value inhibition in the cardiac ion channel. (bvsalud.org)
  • A host of Ca 2+ sources, including distinct subtypes of voltage-dependent calcium channels, intracellular Ca 2+ stores and Ca 2+ -permeable ionotropic neurotransmitter receptors, activate SK channels. (elsevier.com)
  • A) Cartoon of a voltage-gated K + channel showing separate voltage-sensing and pore domains and the S6 activation gate toward the intracellular side of the pore. (rupress.org)
  • This spike in Voltage ( like the spiked EKG graph from heart nerves shown above left ) typically causes nearby channel gates governed by Voltage to open, amplifying the flood of ions and the electrical signal. (myhosting.com)
  • Voltage-dependent K + channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. (frontiersin.org)
  • [13] Because N-type voltage-dependent calcium channels are related to algesia (sensitivity to pain ) in the nervous system, ω-conotoxin has an analgesic effect: the effect of ω-conotoxin M VII A is 100 to 1000 times that of morphine . (rug.nl)
  • Ionic signaling pathways, including voltage-dependent potassium (Kv) channels, are instrumental in antigen-mediated responses of peripheral T cells. (rupress.org)
  • AahG50, the toxic fraction of Androctonus australis hector venom, was studied on human Kv3.1 channels activation, stably expressed in Xenopus oocytes using the two-electrode voltage clamp technique. (archives-ouvertes.fr)
  • The AahG50-induced inhibition of Kv3.1 channels was voltage-dependent, with a gradual increase at lower concentrations and over the voltage range of channels opening. (archives-ouvertes.fr)
  • However, at higher concentrations, the inhibition exhibited voltage dependence only in the first range of channels opening from -20 to +10 mV, but demonstrates a low degree of voltage-dependence when channels are fully activated. (archives-ouvertes.fr)
  • Here, we investigated whether this venom component, called iberiotoxin, would be able to specifically block the FLS potassium channel and reduce the severity of the rheumatoid arthritis in rat models of the disease. (medindia.net)
  • In addition, treatment with iberiotoxin did not induce side effects, such as tremors and incontinence, observed when treating with another channel blocker called paxilline. (medindia.net)
  • It was very exciting to see that iberiotoxin is very specific for the potassium channel in FLS and that it did not seem to affect the channels in other types of cells, which might explain the lack of tremors and incontinence," Tanner said. (medindia.net)
  • We think that this venom component, iberiotoxin, can become the basis for developing a new treatment for rheumatoid arthritis in the future. (medindia.net)
  • This review will focus on current understanding of iberiotoxin-resistant, β4-containing BK channel properties and their function in the CNS. (frontiersin.org)
  • The investigators classified this as the so-called "type II BK channel" which was in contrast to the more conventional iberiotoxin-sensitive type I, fast-gated BK channels. (frontiersin.org)
  • Marie-France Martin-Eauclaire and Pierre E. Bougis, "Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus ," Journal of Toxicology , vol. 2012, Article ID 103608, 9 pages, 2012. (hindawi.com)
  • AmmTX3 (α-KTX15.3) is a peptide that can be isolated from the venom of Androctonus mauretanicus . (wikipedia.org)
  • It is purified from Androctonus australis scorpion venom. (springermedizin.de)
  • Ladjel-Mendil A, Martin-Eauclaire MF, Laraba-Djebari F. Neuropathophysiological effect and immuno-inflammatory response induced by kaliotoxin of androctonus scorpion venom. (springermedizin.de)
  • Inhibition of human Kv3.1 current expressed in Xenopus oocytes by the toxic venom fraction of Androctonus australis hector. (archives-ouvertes.fr)
  • Scorpion venom-derived peptidyl toxins are valuable pharmacological tools for investigating the structure-function relationship of ion channels. (epfl.ch)
  • Several phospholipase A(2) (PLA(2)) neurotoxins from snake venoms can affect acetylcholine release at the neuromuscular junction. (nih.gov)
  • It enables scientists to systematize information on the molecules that block potassium channels. (phys.org)
  • Mitiglinide calcium is a drug for the treatment of type 2 diabetes and it is a highly selective KATP channel antagonist. (csnpharm.com)
  • More importantly, HMIMP was highly selective for the BK channel. (aspetjournals.org)
  • For example, AmmTX3 possibly impairs the consolidation of spatial information and learning strategy through Kv4 channel inhibition, as found within rats in a radial-maze task. (wikipedia.org)
  • Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice. (sigmaaldrich.com)
  • PDF] Structural conservation in prokaryotic and eukaryotic potassium channels. (semanticscholar.org)
  • article{MacKinnon1998StructuralCI, title={Structural conservation in prokaryotic and eukaryotic potassium channels. (semanticscholar.org)
  • [2] [3] Besides its potent ability to block Kv4 channel, AmmTx3 also has a small blocking effect on hERG channels without alteration of the gating kinetics. (wikipedia.org)
  • [1] AmmTX3 has a small blocking effect on hERG channels with an IC50 of 7.9 ± 1.4 µM. (wikipedia.org)
  • MeuKTX potently blocks rKv1.1, rKv1.2 and hKv1.3 channels with 50% inhibitory concentration (IC(50)) of 203.15 ± 4.06 pM, 8.92 ± 2.3 nM and 171 ± 8.56 pM, respectively, but does not affect rKv1.4, rKv1.5, hKv3.1, rKv4.3, and hERG channels even at 2 μM concentration. (epfl.ch)
  • The full peptide was chemically synthesized and properly folded, showing that it blocks the human ERG-channels (HERG) with identical affinity to that of the native peptide. (scielo.org.mx)
  • It paves the way to conduct studies aimed at the identification of the structural motifs of HERG critical for proper channel function. (scielo.org.mx)
  • Terfenadine is a potent open-channel blocker of hERG with a mean IC50 of 204 nM. (csnpharm.com)
  • Tannic acid is a novel hERG channel blocker with IC50 of 3.4 μM. (csnpharm.com)
  • Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam. (bvsalud.org)
  • The human ether-a-go-go-related gene potassium channel (hERG) has an unusual long turret, whose role in recognizing scorpion toxins remains controversial. (biomedcentral.com)
  • The alanine-scanning mutagenesis data indicate that different residue substitutions on hERG channel by alanine decreased the affinities of toxin BmKKx2 by about 10-fold compared with that of wild-type hERG channel, which reveals that channel turrets play a secondary role in toxin binding. (biomedcentral.com)
  • Different from channel turret, the pore region of hERG channel was found to exert the conserved and essential function for toxin binding because the mutant hERG-S631A channel remarkably decreased toxin BmKKx2 affinity by about 104-fold. (biomedcentral.com)
  • Our results not only revealed that channel turrets of hERG channel formed an open conformation in scorpion toxin binding, but also enriched the diversity of structure-function relationships among the different potassium channel turrets. (biomedcentral.com)
  • Poisonous animals such as tarantula spiders, green mamba snakes, or the deathstalker scorpion rely on their venom for efficient defense and precapture strategies. (elifesciences.org)
  • For activity on SKCa channels, the same amino acid residues also affect, directly or indirectly, the recognition of SK channels. (smartox-biotech.com)
  • It has 42 amino-acid residues cross-linked by four disulfide bridges and blocks specifically a potassium channel of the family ether-a-go-go (ERG). (scielo.org.mx)
  • All known Na+ channel specific toxins are composed of 60-76 amino acid residues and stabilized by four disulfide bridges. (diff.org)
  • The K+channel specific toxin are composed of 31-39 amino acid residues long and stabilized by three or four disulfide bonds. (diff.org)
  • Chlorotoxin, specific for Cl − channels, has only 36 amino acid residues, but contains four disulfide bridges. (diff.org)
  • The potassium channel blocker dendrotoxin I was acetylated with acetic anhydride. (strath.ac.uk)
  • In contrast, suramin did not significantly affect the facilitation induced by the potassium channel blocking toxin dendrotoxin I when applied under the same conditions. (nih.gov)
  • Previous studies have shown that CTX binds to the channel on the extracellular side of the pore. (elifesciences.org)
  • In the present study we explore the mechanism underlying the nonconducting phenotype in V478W and compare it to that of W434F, a mutation located in an extracellular region of the pore that is nonconducting because the channel is predominantly found in an inactivated state. (rupress.org)
  • they bind to the extracellular face of the channel and impede passage of ions. (diff.org)
  • This has been interpreted to mean venom in snakes originated more than once as the result of convergent evolution. (texasschoolbusiness.com)
  • and identified 1-[1-hexyl-6-(methyloxy)-1 H -indazol-3-yl]-2-methyl-1-propanone (HMIMP) as a potent and selective BK channel blocker. (aspetjournals.org)
  • In summary, HMIMP is a highly potent and selective BK channel blocker, which can serve as an important tool in the pharmacological study of the BK channel. (aspetjournals.org)
  • Case studies are used to illustrate methods and successes and highlight issues surrounding administration and other important lessons that have been learnt from the development of approved therapeutics based on venoms. (rsc.org)
  • Venoms from marine animals have been recognized as a new emerging source of peptide-based therapeutics. (viewpoint.fr)