Charybdotoxin: A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.Scorpion Venoms: Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Biological Factors: Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.Intermediate-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Large-Conductance Calcium-Activated Potassium Channels: A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position.Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines.Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal CELL MEMBRANES. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Acetylcholine: 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.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Barium Compounds: Inorganic compounds that contain barium as an integral part of the molecule.Scorpions: Arthropods of the order Scorpiones, of which 1500 to 2000 species have been described. The most common live in tropical or subtropical areas. They are nocturnal and feed principally on insects and other arthropods. They are large arachnids but do not attack man spontaneously. They have a venomous sting. Their medical significance varies considerably and is dependent on their habits and venom potency rather than on their size. At most, the sting is equivalent to that of a hornet but certain species possess a highly toxic venom potentially fatal to humans. (From Dorland, 27th ed; Smith, Insects and Other Arthropods of Medical Importance, 1973, p417; Barnes, Invertebrate Zoology, 5th ed, p503)Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)Tetraethylammonium CompoundsKv1.3 Potassium Channel: A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.Endothelium-Dependent Relaxing Factors: Paracrine substances produced by the VASCULAR ENDOTHELIUM with VASCULAR SMOOTH MUSCLE relaxation (VASODILATION) activities. Several factors have been identified, including NITRIC OXIDE and PROSTACYCLIN.Cromakalim: 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)Elapid Venoms: 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.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Picolines: A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Large-Conductance Calcium-Activated Potassium Channel alpha Subunits: The pore-forming subunits of large-conductance calcium-activated potassium channels. They form tetramers in CELL MEMBRANES.Small-Conductance Calcium-Activated Potassium Channels: A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Molsidomine: A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS.Potassium Channels, Voltage-Gated: Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.OxadiazolesEnzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Large-Conductance Calcium-Activated Potassium Channel beta Subunits: The regulatory subunits of large-conductance calcium-activated potassium channels.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Shaker Superfamily of Potassium Channels: Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Muscle, Smooth: 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)Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid: A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Calcium Channel Agonists: Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Benzopyrans: Compounds with a core of fused benzo-pyran rings.Nitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.QuinoxalinesArterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Potassium Chloride: 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.Delayed Rectifier Potassium Channels: A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.Mesenteric Artery, Superior: A large vessel supplying the whole length of the small intestine except the superior part of the duodenum. It also supplies the cecum and the ascending part of the colon and about half the transverse part of the colon. It arises from the anterior surface of the aorta below the celiac artery at the level of the first lumbar vertebra.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Pinacidil: 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)8,11,14-Eicosatrienoic Acid: A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.Microelectrodes: Electrodes with an extremely small tip, used in a voltage clamp or other apparatus to stimulate or record bioelectric potentials of single cells intracellularly or extracellularly. (Dorland, 28th ed)Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels.Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Coronary Vessels: The veins and arteries of the HEART.

RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels. (1/460)

Large-conductance Ca2+- and voltage-activated BK-type K+ channels are expressed abundantly in normal rat pancreatic islet cells and in the clonal rat insulinoma tumor (RINm5f) and hamster insulinoma tumor (HIT) beta cell lines. Previous work has suggested that the Ca2+ sensitivity of BK channels in RIN cells is substantially less than that in HIT cells, perhaps contributing to differences between the cell lines in responsiveness to glucose in mediating insulin secretion. In both RIN cells and normal pancreatic beta cells, BK channels are thought to play a limited role in responses of beta cells to secretagogues and in the electrical activity of beta cells. Here we examine in detail the properties of BK channels in RIN and HIT cells using inside-out patches and whole cell recordings. BK channels in RIN cells exhibit rapid inactivation that results in an anomalous steady-state Ca2+ dependence of activation. In contrast, BK channels in HIT cells exhibit the more usual noninactivating behavior. When BK inactivation is taken into account, the Ca2+ and voltage dependence of activation of BK channels in RIN and HIT cells is essentially indistinguishable. The properties of BK channel inactivation in RIN cells are similar to those of inactivating BK channels (termed BKi channels) previously identified in rat chromaffin cells. Inactivation involves multiple, trypsin-sensitive cytosolic domains and exhibits a dependence on Ca2+ and voltage that appears to arise from coupling to channel activation. In addition, the rates of inactivation onset and recovery are similar to that of BKi channels in chromaffin cells. The charybdotoxin (CTX) sensitivity of BKi currents is somewhat less than that of the noninactivating BK variant. Action potential voltage-clamp waveforms indicate that BK current is activated only weakly by Ca2+ influx in RIN cells but more strongly activated in HIT cells even when Ca2+ current magnitude is comparable. Concentrations of CTX sufficient to block BKi current in RIN cells have no effect on action potential activity initiated by glucose or DC injection. Despite its abundant expression in RIN cells, BKi current appears to play little role in action potential activity initiated by glucose or DC injection in RIN cells, but BK current may play an important role in action potential repolarization in HIT cells.  (+info)

Calcium responses induced by acetylcholine in submucosal arterioles of the guinea-pig small intestine. (2/460)

1. Calcium responses induced by brief stimulation with acetylcholine (ACh) were assessed from the fluorescence changes in fura-2 loaded submucosal arterioles of the guinea-pig small intestine. 2. Initially, 1-1.5 h after loading with fura-2 (fresh tissues), ACh increased [Ca2+]i in a concentration-dependent manner. This response diminished with time, and finally disappeared in 2-3 h (old tissues). 3. Ba2+ elevated [Ca2+]i to a similar extent in both fresh and old tissues. ACh further increased the Ba2+-elevated [Ca2+]i in fresh tissues, but reduced it in old tissues. Responses were not affected by either indomethacin or nitroarginine. 4. In fresh mesenteric arteries, mechanical removal of endothelial cells abolished the ACh-induced increase in [Ca2+]i, with no alteration of [Ca2+]i at rest and during elevation with Ba2+. 5. In the presence of indomethacin and nitroarginine, high-K+ solution elevated [Ca2+]i in both fresh and old tissues. Subsequent addition of ACh further increased [Ca2+]i in fresh tissues without changing it in old tissues. 6. Proadifen, an inhibitor of the enzyme cytochrome P450 mono-oxygenase, inhibited the ACh-induced changes in [Ca2+]i in both fresh and Ba2+-stimulated old tissues. It also inhibited the ACh-induced hyperpolarization. 7. In fresh tissues, the ACh-induced Ca2+ response was not changed by apamin, charybdotoxin (CTX), 4-aminopyridine (4-AP) or glibenclamide. In old tissues in which [Ca2+]i had previously been elevated with Ba2+, the ACh-induced Ca2+ response was inhibited by CTX but not by apamin, 4-AP or glibenclamide. 8. It is concluded that in submucosal arterioles, ACh elevates endothelial [Ca2+]i and reduces muscular [Ca2+]i, probably through the hyperpolarization of endothelial or smooth muscle membrane by activating CTX-sensitive K+ channels.  (+info)

Acetylcholine-induced membrane potential changes in endothelial cells of rabbit aortic valve. (3/460)

1. Using a microelectrode technique, acetylcholine (ACh)-induced membrane potential changes were characterized using various types of inhibitors of K+ and Cl- channels in rabbit aortic valve endothelial cells (RAVEC). 2. ACh produced transient then sustained membrane hyperpolarizations. Withdrawal of ACh evoked a transient depolarization. 3. High K+ blocked and low K+ potentiated the two ACh-induced hyperpolarizations. Charybdotoxin (ChTX) attenuated the ACh-induced transient and sustained hyperpolarizations; apamin inhibited only the sustained hyperpolarization. In the combined presence of ChTX and apamin, ACh produced a depolarization. 4. In Ca2+-free solution or in the presence of Co2+ or Ni2+, ACh produced a transient hyperpolarization followed by a depolarization. In BAPTA-AM-treated cells, ACh produced only a depolarization. 5. A low concentration of A23187 attenuated the ACh-induced transient, but not the sustained, hyperpolarization. In the presence of cyclopiazonic acid, the hyperpolarization induced by ACh was maintained after ACh removal; this maintained hyperpolarization was blocked by Co2+. 6. Both NPPB and hypertonic solution inhibited the membrane depolarization seen after ACh washout. Bumetanide also attenuated this depolarization. 7. It is concluded that in RAVEC, ACh produces a two-component hyperpolarization followed by a depolarization. It is suggested that ACh-induced Ca2+ release from the storage sites causes a transient hyperpolarization due to activation of ChTX-sensitive K+ channels and that ACh-activated Ca2+ influx causes a sustained hyperpolarization by activating both ChTX- and apamin-sensitive K+ channels. Both volume-sensitive Cl- channels and the Na+-K+-Cl- cotransporter probably contribute to the ACh-induced depolarization.  (+info)

Differences in the actions of some blockers of the calcium-activated potassium permeability in mammalian red cells. (4/460)

1. The actions of some inhibitors of the Ca2+-activated K+ permeability in mammalian red cells have been compared. 2. Block of the permeability was assessed from the reduction in the net loss of K+ that followed the application of the Ca2+ ionophore A23187 (2 microM) to rabbit red cells suspended at a haematocrit of 1% in a low potassium solution ([K]0 0.12-0.17 mM) at 37 degrees C. Net movement of K+ was measured using a K+-sensitive electrode placed in the suspension. 3. The concentrations (microM +/- s.d.) of the compounds tested causing 50% inhibition of K+ loss were: quinine, 37 +/- 3; cetiedil, 26 +/- 1; the cetiedil congeners UCL 1269, UCL 1274 and UCL 1495, approximately 150, 8.2 +/- 0.1, 0.92 +/- 0.03 respectively; clotrimazole, 1.2 +/- 0.1; nitrendipine, 3.6 +/- 0.5 and charybdotoxin, 0.015 +/- 0.002. 4. The characteristics of the block suggested that compounds could be placed in two groups. For one set (quinine, cetiedil, and the UCL congeners), the concentration-inhibition curves were steeper (Hill coefficient, nH, > or = 2.7) than for the other (clotrimazole, nitrendipine, charybdotoxin) for which nH approximately 1. 5. Compounds in the first set alone became less active on raising the concentration of K+ in the external solution to 5.4 mM. 6. The rate of K+ loss induced by A23187 slowed in the presence of high concentrations of cetiedil and its analogues, suggesting a use-dependent component to the inhibitory action. This was not seen with clotrimazole. 7. The blocking action of the cetiedil analogue UCL 1274 could not be overcome by an increase in external Ca2+ and its potency was unaltered when K+ loss was induced by the application of Pb2+ (10 microM) rather than by A23187. 8. These results, taken with the findings of others, suggest that agents that block the red cell Ca2+-activated K+ permeability can be placed in two groups with different mechanisms of action. The differences can be explained by supposing that clotrimazole and charybdotoxin act at the outer face of the channel whereas cetiedil and its congeners may block within it, either at or near the K+ binding site that determines the flow of K+.  (+info)

Modulation of chloride, potassium and bicarbonate transport by muscarinic receptors in a human adenocarcinoma cell line. (5/460)

1. Short-circuit current (I(SC)) responses to carbachol (CCh) were investigated in Colony 1 epithelia, a subpopulation of the HCA-7 adenocarcinoma cell line. In Krebs-Henseleit (KH) buffer, CCh responses consisted of three I(SC) components: an unusual rapid decrease (the 10 s spike) followed by an upward spike at 30 s and a slower transient increase (the 2 min peak). This response was not potentiated by forskolin; rather, CCh inhibited cyclic AMP-stimulated I(SC). 2. In HCO3- free buffer, the decrease in forskolin-elevated I(SC) after CCh was reduced, although the interactions between CCh and forskolin remained at best additive rather than synergistic. When Cl- anions were replaced by gluconate, both Ca2+- and cyclic AMP-mediated electrogenic responses were significantly inhibited. 3. Basolateral Ba2+ (1-10 mM) and 293B (10 microM) selectively inhibited forskolin stimulation of I(SC), without altering the effects of CCh. Under Ba2+- or 293B-treated conditions, CCh responses were potentiated by pretreatment with forskolin. 4. Basolateral charybdotoxin (50 nM) significantly increased the size of the 10 s spike of CCh responses in both KH and HCO3- free medium, without affecting the 2 min peak. The enhanced 10 s spike was inhibited by prior addition of 5 mM apical Ba2+. Charybdotoxin did not affect forskolin responses. 5. In epithelial layers prestimulated with forskolin, the muscarinic antagonists atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, both at 100 nM) abolished subsequent 10 microM CCh responses. Following addition of p-fluoro hexahydro-sila-difenidol (pF-HHSiD, 10 microM) or pirenzepine (1 microM), qualitative changes in the CCh response time-profile also indicated a rightward shift of the agonist concentration-response curve; however, 1 microM gallamine had no effect. These results suggest that a single M3-like receptor subtype mediates the secretory response to CCh. 6. It is concluded that CCh and forskolin activate discrete populations of basolateral K+ channels gated by either Ca2+ or cyclic AMP, but that the Cl- permeability of the apical membrane may limit their combined effects on electrogenic Cl- secretion. In addition, CCh activates a Ba2+-sensitive apical K+ conductance leading to electrogenic K+ transport. Both agents may also modulate HCO3- secretion through a mechanism at least partially dependent on carbonic anhydrase.  (+info)

Mechanical stimulation regulates voltage-gated potassium currents in cardiac microvascular endothelial cells. (6/460)

Vascular endothelial cells are constantly exposed to mechanical forces resulting from blood flow and transmural pressure. The goal of this study was to determine whether mechanical stimulation alters the properties of endothelial voltage-gated K+ channels. Cardiac microvascular endothelial cells (CMECs) were isolated from rat ventricular muscle and cultured on thin sheets of silastic membranes. Membrane currents were measured with the use of the whole-cell arrangement of the patch-clamp technique in endothelial cells subjected to static stretch for 24 hours and compared with measurements from control, nonstretched cells. Voltage steps positive to -30 mV resulted in the activation of a time-dependent, delayed rectifier K+current (IK) in the endothelial cells. Mechanically induced increases of 97%, 355%, and 106% at +30 mV were measured in the peak amplitude of IK in cells stretched for 24 hours by 5%, 10%, and 15%, respectively. In addition, the half-maximal voltage required for IK activation was shifted from +34 mV in the nonstretched cells to -5 mV in the stretched cells. Although IK in both groups of CMECs was blocked to a similar extent by tetraethylammonium, currents in the stretched endothelial cells displayed an enhanced sensitivity to inhibition by charybdotoxin. Preincubation of the CMECs with either pertussis toxin or phorbol 12-myristate 13-acetate during the 24 hours of cell stretch did not prevent the increase in IK. The application of phorbol 12-myristate 13-acetate and static stretch stimulated the proliferation of CMECs. Stretch-induced regulation of K+ channels may be important to control the resting potential of the endothelium and may contribute to capillary growth during periods of mechanical perturbation.  (+info)

Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively applied to the endothelium. (7/460)

In rat mesenteric artery, endothelium-derived hyperpolarizing factor (EDHF) is blocked by a combination of apamin and charybdotoxin (ChTX). The site of action of these toxins has not been established. We compared the effects of ChTX and apamin applied selectively to the endothelium and to the smooth muscle. In isometrically mounted arteries, ACh (0.01-10 micrometers), in the presence of indomethacin (2.8 microM) and Nomega-nitro-L-arginine methyl ester (L-NAME) (100 microM), concentration dependently relaxed phenylephrine (PE)-stimulated tone (EC50 50 nM; n = 10). Apamin (50 nM) and ChTX (50 nM) abolished this relaxation (n = 5). In pressurized arteries, ACh (10 microM), applied intraluminally in the presence of indomethacin (2.8 microM) and L-NAME (100 microM), dilated both PE-stimulated (0.3-0.5 microM; n = 5) and myogenic tone (n = 3). Apamin (50 nM ) and ChTX (50 nM) applied intraluminally abolished ACh-induced dilatations. Bath superperfusion of apamin and ChTX did not affect ACh-induced dilatations of either PE-stimulated (n = 5) or myogenic tone (n = 3). This is the first demonstration that ChTX and apamin act selectively on the endothelium to block EDHF-mediated relaxation.  (+info)

Differential effects of pinacidil, cromakalim, and NS 1619 on electrically evoked contractions in rat vas deferens. (8/460)

AIM: To compare the inhibitory action of electrically evoked contractions of rat epididymal vas deferens by pinacidil (Pin), cromakalim (Cro), and NS 1619. METHODS: Monophasic contractions were evoked by electric field stimulation in rat isolated epididymal half of vas deferens. RESULTS: Newly developed ATP-sensitive K+ channel openers, Pin and Cro, concentration-dependently reduced the electrically evoked (0.3 Hz, 1 ms pulse duration, 60 V) contractions and glibenclamide but not charybdotoxin antagonized the inhibitory effects of both agents. Pin shifted the concentration-response curve for norepinephrine to the right with reducing the magnitude of the maximum contraction in a glibenclamide-sensitive fashion. The large-conductance Ca(2+)-activated K+ channel opener, NS 1619, inhibited the electrically evoked contractions in a concentration-dependent manner. Charybdotoxin (100 nmol.L-1) partially reduced the effect of NS 1619 but glibenclamide (10 mumol.L-1) showed no effect. None of these 3 agents affected the basal tension. CONCLUSION: Both ATP-sensitive and Ca(2+)-activated K+ channels presented in vas deferens smooth muscles involved in regulation of muscle contractility.  (+info)

Charybdotoxin occludes the pore of calcium-activated voltage-gated shaker K+ channels by binding to one of four independent, overlapping binding sites.[6][7] It binds both to the open and the closed states. In addition, the block is enhanced as the ionic strength is lowered.[8] This block occurs as the Asn 30 on the CTX interacts with the Asp 381 on the K+ channel.[9] The blockade of K+ channels by the charybdotoxin peptide causes neuronal hyperexcitability. Mutations of the Lys31Gln and the Asn30Gln had the effect of lessening the CTX block of the pore on the shaker channel.[9] ...
The first study to inject synaptic noise in cortical neurons using dynamic-clamp and artificially recreate high-conductance states was proposed about 6 years ago (Destexhe et al., 2001), and was followed by a number of studies which investigated different aspects of high-conductance states using this technique (Chance et al., 2002; Prescott and Dekoninck, 2003; Fellous et al., 2003; Shu et al., 2003; Wolfart et al., 2005). To this end, one needs first to generate an appropriate model of stochastic synaptic activity because thousands of synapses releasing randomly cannot be simulated in real time. A stochastic "point-conductance" model was proposed (Destexhe et al., 2001), which consists in two fluctuating synaptic conductances described by one-variable stochastic processes (Fig. 6A; red and blue traces). These processes are adjusted to match the total conductance seen at the soma during background activity. These conductances are then injected in dynamic-clamp (Fig. 6A) in order to reproduce the ...
High purity synthetic Margatoxin (#STM-325) (CAS 145808-47-5) is a biologically active Kv1.3 and Kv1.6 channel blocker. 100% net peptide content. New lots are biologically tested. Free samples available. Lyophilized powder. Worldwide shipping at room temp. Alomone Labs is your top supplier for K+ channel research!
TY - JOUR. T1 - The contribution of d-tubocurarine-sensitive and Apamin-sensitive K-channels to EDHF-mediated Relaxation of Mesenteric Arteries from eNOS-/- Mice. AU - Chen, Xiaoliang. AU - Li, Yang. AU - Hollenberg, Morley. AU - Triggle, Christopher. AU - Ding, Hong. PY - 2012/5. Y1 - 2012/5. N2 - The nature of the potassium channels involved in determining endothelium-derived hyperpolarizing factor-mediated relaxation was investigated in first-order small mesenteric arteries from male endothelial nitric oxide synthase (eNOS-/-)-knockout and control (+/+) mice. Acetylcholine-induced endothelium-dependent relaxation of small mesenteric arteries of eNOS-/- was resistant to N-nitro-L-arginine and indomethacin and the guanylyl cyclase inhibitor, 1H-(1,2,4) oxadiazolo (4,3-a) quinoxalin-1-one. Apamin and the combination of apamin and iberiotoxin or apamin and charybdotoxin induced a transient endothelium-dependent contraction of small mesenteric arteries from both eNOS-/- and +/+ mice. ...
Based on current evidence, the term of endothelium-derived hyperpolarising factor should represent a mechanism rather than a specific factor. The mechanism(s) of endothelium-dependent hyperpolarization (i.e., EDHF-mediated relaxation) seems to be heterogeneous depending on several factors (e.g., size and vascular bed), surrounding environment (oxidative stress, hypercholesterolemia) and demand (compensatory). Different endothelial mediators or pathways involved in EDHF-mediated relaxation may also work simultaneously and/or substitute each other. It implies a reasonable physiological sense, although to some extent and when EDHF acts as backup mechanism for endothelium-dependent relaxation in the present of compromised NO contribution. Thus, alternatives for EDHF-typed responses (H2O2, K+ etc.) will provide a guarantee for compensation of endothelial function. However, once the involvement of a certain endothelium-derived vasodilator for a given vascular bed is confirmed, it is preferred that ...
How is intermediate-conductance K+ channel abbreviated? i-K+ stands for intermediate-conductance K+ channel. i-K+ is defined as intermediate-conductance K+ channel rarely.
ATP-elicited delayed K+ current was not inhibited by a cocktail of K+ channel blockers (4-AP, TEA, apamin, charybdotoxin, glibenclamide). The amplitude of the delayed K+ current decreased after the reduction of extracellular pH from 7.4 to 6.5. These two characteristics suggest that this current could be carried by the TASK subfamily of twin-pore potassium channels (K2P). Purinergic agonists including dATP, but not ADP, activated the delayed K+ current, indicating that P2Y11 is the likely receptor involved in its activation. The PKC activator phorbol ester 12,13-didecanoate stimulated this current. In addition, the PKC inhibitor Gö 6850 partially inhibited it. Real-time quantitative PCR showed that the genes encoding TASK-1 and TASK-2 are expressed. Conclusion ...
TY - JOUR. T1 - Endothelium-derived hyperpolarizing factor(s). T2 - Species and tissue heterogeneity. AU - Triggle, C. R.. AU - Dong, H.. AU - Waldron, G. J.. AU - Cole, W. C.. PY - 1999/1/1. Y1 - 1999/1/1. N2 - 1. Endothelium-derivcd relaxing factor is almost universally considered to be synonymous with nitric oxide (NO); however, it is now well established that at least two other chemically distinct species (prostacyclin (PGI2) and a hyperpolarizing factor) may also contribute to endothelium-dependent relaxation. 2. Only relatively few studies have provided definitive evidence that an endothelium-derived hyperpolarizing factor (EDHF), which is neither NO nor PGI2, exists as a chemical mediator. 3. There is a lack of agreement as to the likely chemical identity of this putative factor. Some evidence suggests that EDHF may be a cytochrome P450-derived arachidonic acid product, possibly an epoxyeicosatrienoic acid (EET); conflict-ing evidence supports an endogenous cannabinoid as the mediator and ...
Kaliotoxin (KTX) inhibits potassium flux through the Kv1.3 voltage-gated potassium channel and calcium-activated potassium channels by physically blocking the channel-entrance and inducing a conformational change in the K+-selectivity filter of the channel. KTX is a neurotoxin derived from the scorpion Androctonus mauretanicus mauretanicus, which is found in the Middle East and North Africa. (Crest M et al.) Kaliotoxin is a 4-kDa polypeptide chain, containing 38 amino acids. The formula is C171H283N55O49S8. The sequence has a large homology with iberiotoxin from Buthus tumulus, charybdotoxin from Leiurus quinquestriatus and noxiustoxin from Centruroides noxius. An Important site of the toxin is the K27 side chain (a lysine at place 27 of the protein sequence), which enters the pore and protrudes into the selectivity filter of the channel. (Lange A et al., Korukottu J et al.) KTX binds to the Kv1.3 voltage-gated potassium channel and the Calcium-activated potassium channels (BK channels). (Lange ...
Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013 ...
MGI protein superfamily detail pages represent the protein classification set for a homeomorphic superfamily from the Protein Information Resource SuperFamily (PIRSF) site.. Mouse superfamily members are shown with links to their corresponding HomoloGene Classes. Note that pseudogenes are included in PIRSF families but not in orthology sets used here. You can select a given mouse superfamily member and download (or forward to NCBI BLAST) FASTA formatted protein sequences of that mouse gene and its mouse, human and rat homologs, as defined in the corresponding HomoloGene Class. The numbers of mouse, human and rat genes in the HomoloGene Class are shown. You can also "Select all" mouse superfamily members to obtain their protein sequences and the protein sequences for all mouse, human and rat homologs of the mouse superfamily members.. The number of protein sequences returned does not always match the numbers of homologs shown, because the same protein sequence can be associated with multiple ...
The endothelium has emerged as an important regulator of vascular tone.1 2 3 Several soluble mediators released by the endothelium are involved in these vascular effects. These mediators include prostacyclin, EDRF or NO, and EDHF. The activity of EDHF may be distinguished from NO in that EDHF activity is blocked by inhibitors of Ca2+-activated K+ channels, such as TEA or charybdotoxin, or by high [K+]o but is not blocked by arginine analogues that inhibit NOS or glibenclamide, an inhibitor of ATP-sensitive K+ channels.9 14 17 18 Relaxations mediated by EDRF are blocked by arginine analogues. In small coronary arteries, methacholine causes endothelium-dependent relaxations and endothelium-dependent hyperpolarization of smooth muscle cells.5 14 15 16 17 18 These relaxations are blocked by TEA and high [K+]o. Thus, it has been proposed that methacholine stimulates coronary endothelial cells to release EDHF, which acts on coronary smooth muscle cells to open K+ channels, hyperpolarize the cell ...
Maurotoxin (MTX) is a 34-residue toxin that was isolated initially from the venom of the scorpion Scorpio maurus palmatus. Unlike the other toxins of the α-KTx6 family (Pi1, Pi4, Pi7, and HsTx1), MTX exhibits a unique disulfide bridge organization of the type C(1) C(5) , C(2) C(6) , C(3) C(4) , and C(7) C(8) (instead of the conventional C(1) C(5) , C(2) C(6) , C(3) C(7) , and C(4) C(8) , herein referred to as Pi1-like) that does not prevent its folding along the classic α/β scaffold of scorpion toxins. MTX(Pi1) is an MTX variant with a conventional pattern of disulfide bridging without any primary structure alteration of the toxin. 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. 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
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apamin definition: Noun (uncountable) 1. (biochemistry) A neurotoxin originally isolated from Apis mellifera, the Western honey bee....
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin (By similarity).
In WT mice, endothelium-dependent relaxations of small mesenteric arteries were mainly mediated by EDHF, whereas those of the aorta were mediated by NO, a finding that is consistent with our previous studies (2, 4, 14). Interestingly, EDHF-mediated relaxations were progressively reduced in accordance with the number of disrupted NOS genes in mesenteric arteries and were absent in n/i/eNOS−/− mice, indicating that EDHF-mediated relaxations are totally mediated by the endothelial NOSs system in mouse mesenteric arteries.. In this study, after the classical definition of EDHF (1-3), we evaluated EDHF-mediated responses in mouse mesenteric arteries in the presence of indomethacin and l-NNA. It is known that eNOS generates superoxide anions under normal conditions from reductase domain and only when uncoupled (e.g., BH4 and/or l-arginine depletion) from the oxidase domain, and that l-arginine analogues only inhibit the latter process (40). Indeed, we were able to demonstrate that endothelial ...
TY - JOUR. T1 - Expression of intermediate-conductance, Ca2+-activated K+ channel (KCNN4) in H441 human distal airway epithelial cells. AU - Wilson, Stuart M.. AU - Brown, Sean G.. AU - McTavish, Niall. AU - McNeill, R. P.. AU - Husband, E. M.. AU - Inglis, Sarah K.. AU - Olver, Richard E.. AU - Clunes, M. T.. PY - 2006/6/9. Y1 - 2006/6/9. N2 - Electrophysiological studies of H441 human distal airway epithelial cells showed that thapsigargin caused a Ca2+-dependent increase in membrane conductance (GTot) and hyperpolarization of membrane potential (Vm). These effects reflected a rapid rise in cellular K+ conductance (GK) and a slow fall in amiloride-sensitive Na+ conductance (GNa). The increase in GTot was antagonized by Ba2+, a nonselective K+ channel blocker, and abolished by clotrimazole, a KCNN4 inhibitor, but unaffected by other selective K+ channel blockers. Moreover, 1-ethyl-2-benzimidazolinone (1-EBIO), which is known to activate KCNN4, increased GK with no effect on GNa. RT-PCR-based ...
We studied the role of K+ channels and Na+,K+-ATPase in the presynaptic inhibitory effects of prostaglandin E1 (PGE1) and PGE2 on the adrenergic responses of human vas deferens. Furthermore, we determined the effects of increasing extracellular K+ concentrations ([K+]o) and inhibition of Na+,K+- ATPase on neurogenic and norepinephrine-induced contractile responses. Ring segments of the epididymal part of the vas deferens were taken from 45 elective vasectomies and mounted in organ baths for isometric recording of tension. The neuromodulatory effects of PGEs were tested in the presence of K+ channel blockers. PGE1 and PGE2 (10_8 to 10_6 M) induced inhibition of adrenergic contractions. The presence of tetraethylammonium (10_3 M), charybdotoxin (10_7 M), or iberiotoxin(10_7 M), prevented the inhibitory effects of PGE1 and PGE2 on the adrenergic contraction. Botx glibenclamide (10_5 M) and apamin (10_6 M) failed to antagonize PGE1 and PGE2 effects. Raising the [K+]o from 15.8 mM to 25.8 mM caused ...
View mouse Kcnmb4 Chr10:116417861-116473542 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
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The amino terminal region of Pi3 lacks three residues when compared to other toxins of the same family e.g. charybdotoxin. ... The three-dimensional structure of Pi3 is similar to other potassium channel blocking toxins like Charybdotoxin, because it has ... Miller C (July 1995). "The charybdotoxin family of K+ channel-blocking peptides". Neuron. 15 (1): 5-10. doi:10.1016/0896-6273( ...
Bontems, F.; Roumestand, C.; Gilquin, B.; Ménez, A.; Toma, F. (1991). "Refined structure of charybdotoxin: Common motifs in ... Gao, Y. D.; Garcia, M. L. (2003). "Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: ... 2003). "Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: selectivity between voltage-gated and ... Other toxins found in this species include charybdotoxin (CTX). CTX is a close homologue of Agitoxin. Agitoxin can be purified ...
Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles". Biophys. J. 73 (4): 1717-1727. ... charybdotoxin or hisactophilin. Orientations and penetration depths of many amphitropic proteins and peptides in membranes are ... cationic toxins such as charybdotoxin, and specific membrane-targeting domains such as some PH domains, C1 domains, and C2 ...
"Interaction of charybdotoxin with permeant ions inside the pore of a K+ channel". Neuron. 9 (2): 307-313. doi:10.1016/0896-6273 ... Goldstein, S.A.; Miller, C. "Mechanism of charybdotoxin block of a voltage-gated K+ channel". Biophysical Journal. 65 (4): 1613 ...
NTX is similar in sequence to the margatoxin (79% identity), the kaliotoxin (51% identity), the charybdotoxin (49% identity), ... "Charybdotoxin and noxiustoxin, two homologous peptide inhibitors of the K+(Ca2+) channel". FEBS Letters. 226 (2): 280-284. doi: ...
Miller C (December 1988). "Competition for block of a Ca2(+)-activated K+ channel by charybdotoxin and tetraethylammonium". ...
LbTX displays 57% sequence homology with charybdotoxin and 70% sequence homology with iberiotoxin. LbTX contains a β-sheet ...
The complete amino acid sequence has been defined and it displays 68% sequence homology with charybdotoxin. Iberiotoxin binds ...
In this state BK channels can still be inhibited by one of their inhibitors, like charybdotoxin (CTX). Opening of the BK ...
The 37 amino acid peptide belongs to the charybdotoxin sub-family (αKTx1) and was numbered member 11. αKTx1.11 revealed ...
... is also known as Potassium channel toxin alpha-KTx 1.2, Charybdotoxin-2, ChTX-Lq2, ChTx-d, Toxin 18-2 or Lqh 18-2. The name ... Lq2 contains the classical scorpion toxin alpha-beta scaffold and is structurally similar to the neurotoxin Charybdotoxin (CTX ...
... and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5562-7. doi: ...
... and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin". Proceedings of the National Academy of Sciences of ...
The sequence has a large homology with iberiotoxin from Buthus tumulus, charybdotoxin from Leiurus quinquestriatus and ...
... similarity of sapecin B to charybdotoxin". Biochem. J. 291: 275-279. PMC 1132513 . PMID 8471044. Cociancich S, Bulet P, ...
This suggests that TmTx does not have an effect on SK channels or charybdotoxin-sensitive IK channels (calcium-activated ...
Neurotoxins in L. quinquestriatus venom include: Chlorotoxin Charybdotoxin Scyllatoxin Agitoxins types one, two and three The ...
... face of the α-helix is anchored to the β-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin ...
... contains three disulfide bridges.[5] Mode of action[edit]. Charybdotoxin occludes the pore of calcium-activated ... Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker ... The Charybdotoxin family of scorpion toxins is a group of small peptides that has many family members, such as the pandinotoxin ... Scorpions such as the deathstalker paralyze their prey by injecting a potent mix of peptide toxins.[4] Charybdotoxin, a 37 ...
... charybdotoxin, noxiustoxin, anuroctoxin) and sea anemone (ShK, ShK-F6CA, ShK-186, ShK-192, BgK), and by small molecule ...
Toxins that affect the Shaker K channel include: Agitoxin Charybdotoxin Iberiotoxin Pandinotoxin 6-bromo-2-mercaptotryptamine ( ...
... a genetic disorder Charybdotoxin, a toxin found in scorpion venom Chemotherapy, treatment of cancer with cytotoxic drugs ...
... charybdotoxin MeSH D20.888.065.870 --- spider venoms MeSH D20.888.065.870.650 --- omega-agatoxin iva MeSH D20.888.065.970 --- ...
... and the scorpion venoms tamapin and charybdotoxin (ChTx), all via competitive antagonism for access to the mouth of the pore ...
... such as charybdotoxin (44%), kaliotoxin (54%), iberiotoxin (41%) and noxiustoxin (79%), which are also derived from scorpion ...
Charybdotoxin (100 nM) did not significantly alter the action potential duration or AHP amplitude but reduced the AHP duration ... charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. Ionomycin (1-10 μM) increased BK channel ... charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. Ionomycin (1-10 μM) increased BK channel ...
... or tubocurarine with charybdotoxin but not by apamin, charybdotoxin, scyllatoxin, or tubocurarine alone. These data indicate ... or tubocurarine with charybdotoxin but not by apamin, charybdotoxin, scyllatoxin, or tubocurarine alone. These data indicate ... or tubocurarine with charybdotoxin but not by apamin, charybdotoxin, scyllatoxin, or tubocurarine alone. These data indicate ... or tubocurarine with charybdotoxin but not by apamin, charybdotoxin, scyllatoxin, or tubocurarine alone. These data indicate ...
... and charybdotoxin (0.1 mu M) also failed to affect the venom-induced relaxations. Similarly, the Kt channel blocker ...
Charybdotoxin contains three disulfide bridges.[5] Mode of action[edit]. Charybdotoxin occludes the pore of calcium-activated ... Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker ... The Charybdotoxin family of scorpion toxins is a group of small peptides that has many family members, such as the pandinotoxin ... Scorpions such as the deathstalker paralyze their prey by injecting a potent mix of peptide toxins.[4] Charybdotoxin, a 37 ...
Charybdotoxin (ChTX), a K+ channel blocker, depolarizes human peripheral T lymphocytes and renders them insensitive to ... mechanism of the antiproliferative effect of charybdotoxin. R J Leonard, M L Garcia, R S Slaughter, and J P Reuben ... mechanism of the antiproliferative effect of charybdotoxin ... mechanism of the antiproliferative effect of charybdotoxin. R J ... mechanism of the antiproliferative effect of charybdotoxin ...
charybdotoxin-GLU32 analog ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental ...
... ... and charybdotoxin (CTX) and to gain new insights into the molecular determinants that define the interaction of these pore- ...
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Buy Charybdotoxin - an affordable, high quality KCa channel inhibitor from Hello Bio, a trusted supplier for life science ... References for Charybdotoxin. *. Purification, sequence, and model structure of charybdotoxin, a potent selective inhibitor of ... Electrostatic interaction between charybdotoxin and a tetrameric mutant of Shaker K(+) channels.. Thompson J et al (2000) ... Charybdotoxin and margatoxin acting on the human voltage-gated potassium channel hKv1.3 and its H399N mutant: an experimental ...
Charybdotoxin Binding in the IKs Pore Demonstrates Two MinK Subunits in Each Channel Complex. Haijun Chen, Leo A. Kim, Sindhu K ... Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. @article{ ... Miller1985CharybdotoxinAP, title={Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian ...
Charybdotoxin - SBP0166 - Charybdotoxin MW: 4295.95 pGlu-Phe-Thr-Asn-Val-Ser-Cys-Thr-Thr-Ser-Lys-Glu-Cys-Trp-Ser-Val-Cys-Gln- ... SBP0166 - Charybdotoxin. MW: 4295.95. pGlu-Phe-Thr-Asn-Val-Ser-Cys-Thr-Thr-Ser-Lys-Glu-Cys-Trp-Ser-Val-Cys-Gln-Arg-Leu-His-Asn- ...
Charybdotoxin. KCa2+ channel blocker. Charybdotoxin (ChTx) is a 37 amino acid peptide isolated from the venom of the scorpion ... Mechanism of charybdotoxin block of a voltage-gated K+ channel.. Charybdotoxin block of a Shaker K+ channel was studied in ... The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues mediating molecular recognition.. Charybdotoxin ... Charybdotoxin (ChTX), a protein present in the venom of the scorpion Leiurus quinquestriatus var. hebraeus, has been purified ...
Charybdotoxin (ChTX; 10 nM), which blocks large conductance Ca(2+)-activated K(+)-channel function, completely blocked and ...
100 nM charybdotoxin (CBX); 100 nM apamin plus 100 nM charybdotoxin (Ap + CBX); or 100 nM apamin plus 50 nM iberiotoxin (Ap + ...
Indo, indomethacin; CTx, charybdotoxin; Apm, apamin. *, P , 0.05; **, P , 0.01. Relative contribution of EDHF in male (I) and ... and a combination of charybdotoxin and apamin, respectively (14, 21). To examine the effect of NOS uncoupling on EDHF-mediated ... but were markedly inhibited by a combination of 100 nM charybdotoxin (an inhibitor of large- and intermediate-conductance ...
A charybdotoxin-insensitive conductance in human T lymphocytes: T cell membrane potential is set by distinct K+ channels. J. ... Ca2+ induces charybdotoxin-sensitive membrane potential changes in rat lymphocytes. Am. J. Physiol. 257:C197-C206. ... Charybdotoxin (CTX)* and margatoxin (MgTX), which block the predominant voltage-dependent potassium (Kv) channel (Kv1.3) of ... charybdotoxin; DTX-I, dendrotoxin-I; DTX-K, dendrotoxin K; Kv channel, voltage-gated potassium channel; MgTX, margatoxin; Vm, ...
The fluoranthene-induced modulations of these anion transporters were counteracted by charybdotoxin (ChTx, a hIK-1 channel ... charybdotoxin; DEP, diesel exhaust particle; DNDS, 4,4′-dinitrostilbene-2,2′-disulfonic acid; FLT, fluoranthene; ISO, ...
Lack of Effect of Charybdotoxin on RPV KDR. Charybdotoxin was previously shown to block homomultimeric Kv1.2 channels27-29 but ... as well as a lack of sensitivity to charybdotoxin. Kv1.5 channels are not affected by charybdotoxin,28,29 but we found that RPV ... RPV KDR current was not affected by charybdotoxin block of Kv1.2 homotetramers27-29; however, we found that heteromultimeric ... Finally, native KDR current was found to be insensitive to charybdotoxin-block of homomultimeric Kv1.2 channels. The findings ...
Charybdotoxin (10(-7) M), an inhibitor of Ca(2+)-activated K+ channels, almost doubled [Ca2+]i, whereas glibenclamide (10(-5) M ... The average resting membrane potential (RMP) was -36 +/- 3 mV and could be depolarized by charybdotoxin (100 nM) or ... charybdotoxin (CTX; preferential high-conductance Ca2+-dependent K+-channel blocker), apamin (Apa; low-conductance Ca2+- ... the K+ channel blockers tetraethylammonium or charybdotoxin, or blockade of Ca2+ entry with lanthanum decreased [Ca2+]i by 54- ...
Animals were pretreated with glibenclamide (GLIB; 10 mg/kg, i.p.), apamin (APA; 0.04 mg/kg, i.p.), charybdotoxin (CHAR; 0.02, i ... Figure 7: Effect of glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride on MECN-induced antinociception in ... charybdotoxin (CHAR; an inhibitor of large conductance Ca2+-activated K+ channels, 0.02 mg/kg, i.p.), or tetraethylammonium ... charybdotoxin, and tetraethylammonium chloride). The results demonstrated that the orally administered MECN (100, 250, and 500 ...
... only HuKIV has charybdotoxin sensitivity. Differences are observed between the pharmacological sensitivities of human channels ...
Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate ... and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin.". Meera P., Wallner M., Toro L.. Proc. Natl. Acad. ... Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate ...
Mechanism of charybdotoxin block of the high-conductance, Ca2+-activated K+ channel. J. Gen. Physiol. 91, 335-349 (1988).. ... Interaction of charybdotoxin with permeant ions inside the pore of a K+ channel. Neuron 9, 307-313 (1992).. ... Mechanism of charybdotoxin block of a voltage-gated K+ channel. Biophys. J. 65, 1613-1619 (1993).. ... Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor. Science 245, 1382-1385 ( ...
Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex.. Yu L, Sun C, Song D, Shen J, Xu N ...
Besides iberiotoxin, BK α+β4 channels are also resistant to charybdotoxin (Meera et al., 2000) and slotoxin (Garcia-Valdes et ... Miller C, Moczydlowski E, Latorre R, and Phillips M (1985) Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ ... Several widely used BK channel inhibitors, such as iberiotoxin (Galvez et al., 1990), charybdotoxin (Miller et al., 1985), and ... charybdotoxin, and slotoxin (Meera et al., 2000; Garcia-Valdes et al., 2001; Lippiat et al., 2003). Nonpeptide, alkaloid BK ...
  • The Charybdotoxin family of scorpion toxins is a group of small peptides that has many family members, such as the pandinotoxin , derived from the venom of scorpion Pandinus imperator . (wikipedia.org)
  • The amino terminal region of Pi3 lacks three residues when compared to other toxins of the same family e.g. charybdotoxin. (wikipedia.org)
  • However, when 1-ethyl-2-benzimidazolinone (EBIO) was used to stimulate chloride secretion, XE991 was ineffective unless charybdotoxin was also present. (aspetjournals.org)
  • K DR currents were not sensitive to charybdotoxin, which blocks homotetrameric Kv1.2 channels. (ahajournals.org)
  • One face of the α-helix is anchored to the β-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin family (R-K toxins). (wikipedia.org)
  • The three-dimensional structure of Pi3 is similar to other potassium channel blocking toxins like Charybdotoxin, because it has three disulphide bridges that stabilize two strands of beta sheet structures and a short alpha helix. (wikipedia.org)