Inhibition by multivalent cations of contraction induced by chinese cobra venom cardiotoxin in guinea pig papillary muscle

Abstract

The effects of cardiotoxin (CTX), purified from the venom of Chinese Cobra ( Naja naja atra) by a three-step chromatography, on the contractile responses of isolated guinea pig papillary muscle preparation and its antagonism by lanthanum ion (La 3+) and divalent cations were examined. CTX induced tonic contraction following a transient augmentation of electrically evoked rhythmic contractions, which is similar to that seen in perfused heart preparation. Multivalent cations, La 3+, Ca 2+, Mn 2+ and Mg 2+, concentration-dependently blocked CTX-induced contraction. In Ca 2+-free medium, CTX did not induce contraction and CTX-induced contraction was not modified in Na +-free medium. Nifedipine (1 μ mol L ), effectively blocked KC1-induced contracture, but only partially inhibited CTX-induced contraction; thus suggesting that Ca 2+ influx induced by CTX utilizes channels other than L-type Ca 2+ channels. These cations may compete with CTX for the negatively charged membrane binding site which is responsible for the modulation of Ca 2+ movement.