Electrophysiological studies of myotoxin a, isolated from prairie rattlesnake (Crotalus viridis viridis) venom, on murine skeletal muscles.
Myotoxin a reduced the resting membrane potential of mouse and rat diaphragms from about -80 mV to -60 mV, induced spontaneous repetitive firing and enhanced the contractile force in response to single stimulations. The depolarizing effect was reversed noncompetitively by tetrodotoxin, local anesthetics or low Na+ solution, but was augmented by ouabain or low Cl-solution while being unaffected by high K+ solution or electrical stimulation of the muscle. The duration of muscle action potential was prolonged by only 20-30%, whereas the rate of rise (dV/dt) was unaffected. About a 40% increase of membrane conductance was observed, be abolished by the Na+-channel blocker tetrodotoxin. By contrast, K+ conductance was unaffected. Effects on caffeine-induced contracture, quantal release of neurotransmitter and the amplitude of miniature endplate potential were not appreciably affected. These effects of myotoxin a indicate that the toxin affects the muscle, but not the nerve, by acting specifically on the Na+-channel of the sarcolemma or T-tubule, like crotamine, rather than on the sarcoplasmic reticulum. The effects of sea anemone toxin II on the Na+-channel (marked depolarization and prolongation of action potential) could not be prevented by saturating the muscle with myotoxin a. On the other hand, the effect of veratridine, a member of another group of toxins acting on the Na+-channel, was enhanced. These results suggest that myotoxin a acts on the Na+-channel at a site which is discrete from those of tetrodotoxin, veratridine and sea anemone toxin II.
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Hong
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Chang
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D003064:Cnidarian Venoms / Q000494:pharmacology; D003435:Crotalid Venoms / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects; D004594:Electrophysiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D051381:Rats; D012508:Sarcolemma / Q000187:drug effects; D014701:Veratridine / Q000494:pharmacology
D003064:Cnidarian Venoms; D003435:Crotalid Venoms; D007473:Ion Channels; C028800:toxin II (Anemonia sulcata); C018932:myotoxin A; D014701:Veratridine; C010563:crotamine