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

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 (La3+) 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, La3+, Ca2+, Mn2+ and Mg2+, 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 mumol/L), effectively blocked KCl-induced contracture, but only partially inhibited CTX-induced contraction; thus suggesting that Ca2+ influx induced by CTX utilizes channels other than L-type Ca2+ channels. These cations may compete with CTX for the negatively charged membrane binding site which is responsible for the modulation of Ca2+ movement.