Effect of crotamine, a toxin of South American rattlesnake venom, on the sodium channel of murine skeletal muscle.
1 Crotamine (0.5 mug/ml) augmented the single twitch response of the rat and mouse isolated diaphragm to direct stimulation and prolonged the time course of contraction. At higher doses (10 to 50 mug/ml), contracture was observed with spontaneous fibrillation.2 The resting membrane potential of diaphragm was rapidly depolarized to about -50 mV within 5 minutes. No increase of depolarization occurred on prolongation of the incubation time or increase of crotamine concentration from 0.5 mug/ml to 50 mug/ml. The effect was not reversed by washing.3 Tetrodotoxin, low Na(+) (12 mM), Ca(2+) (10 mM) and procaine (1 mM) prevented the crotamine-depolarization. However, depolarization resumed when crotamine and the antagonists were removed.4 Low Cl(-) (8.5 mM) and pretreatment with ouabain enhanced depolarization by crotamine.5 High K(+) (25 to 50 mM) prevented the further depolarization by crotamine and the membrane potential was restored to normal on washout of crotamine with normal Tyrode solution.6 Effective membrane resistance was decreased by about 50% by crotamine.7(24)Na-influx of the rat diaphragm was increased by crotamine. (42)K-influx was slightly increased if tetrodotoxin was also present but was decreased in the absence of tetrodotoxin.8 No effect on the miniature and evoked endplate potential of the rat diaphragm was observed. Skeletal muscles from frog and chick were not affected.9 It is inferred that crotamine acts on a molecule regulating the Na(+) - permeability of the Na(+) channel of murine muscles. It is proposed that extracellular K(+) depresses the permeability of the Na(+) channel by acting on the same regulator molecule.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002712:Chlorides / Q000502:physiology; D003435:Crotalid Venoms / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D003435:Crotalid Venoms; D013779:Tetrodotoxin; D011343:Procaine; D010042:Ouabain; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D002118:Calcium