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.