Contracture induction by snake venom cardiotoxin in skeletal muscle from humans and rats

Contracture responses to cardiotoxin (CTX) from Naja naja kaouthia venom were investigated in rat and human skeletal muscle of similar fiber type distribution to determine species differences in mechanism of action. Rat diaphragm strips and human vastus lateralis preparations were directly stimulated in a tissue bath. The calcium dependence of toxin action, synergism between CTX and phospholipase A2 (PLA2) activity and roles of Na+ + K+-ATPase activity and the sarcoplasmic reticulum Ca2+ stores in contracture induction were examined. The threshold of contracture to CTX was decreased in human and rat muscle when Sr2+ was substituted for Ca2+ in the bathing medium. In rat, but not in human muscle the threshold of contracture to CTX was decreased in a medium in which Ca2+ had been omitted. The decrease in contracture threshold may relate to toxin binding. The maximum height of contracture for preparations from humans, but not for those from rats was considerably depressed in a medium in which Ca2+ had been omitted. Exogenously added bee venom PLA2 acts synergistically with CTX in skeletal muscle in a manner similar to that in erythrocytes. Ouabain (100 microM) did not elicit contractures in any of the media tested nor affect CTX-induced contractures in Sr2+-containing medium. Dantrolene antagonized CTX-induced contractures, suggesting a role for Ca2+ derived from the sarcoplasmic reticulum in CTX action. The species difference in CTX action may reflect differences in the relative contribution of Ca2+ from the sarcolemma and sarcoplasmic reticulum to the contracture.