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

Abstract

J. E. Fletcher and F. H. Lizzo. Contracture induction by snake venom cardiotoxin in skeletal muscle from humans and rats. Toxicon 25, 1003 – 1010, 1987. — 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 A 2 (PLA 2) activity and roles of Na + + K +-ATPase activity and the sarcoplasmic reticulum Ca 2+ stores in contracture induction were examined. The threshold of contracture to CTX was decreased in human and rat muscle when Sr 2+ was substituted for Ca 2+ in the bathing medium. In rat, but not in human muscle the threshold of contracture to CTX was decreased in a medium in which Ca 2+ 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 Ca 2+ had been omitted. Exogenously added bee venom PLA 2 acts synergistically with CTX in skeletal muscle in a manner similar to that in erythrocytes. Ouabain (100 μM) did not elicit contractures in any of the media tested nor affect CTX-induced contractures in Sr 2+-containing medium. Dantrolene antagonized CTX-induced contractures, suggesting a role for Ca 2+ derived from the sarcoplasmic reticulum in CTX action. The species difference in CTX action may reflect differences in the relative contribution of Ca 2+ from the sarcolemma and sarcoplasmic reticulum to the contracture.