Effects of purified cardiotoxins from the Thailand cobra (Naja naja siamensis) on isolated skeletal and cardiac muscle preparations

Four polypeptides were isolated by non-exchange chromatography from the crude cardiotoxin fraction of Thailand cobra (Naja naja siamensis) venom. Fraction I and 71 amino acid residues including 1 tryptophan, while fractions, II, III and IV had 60 amino acids and no tryptophan. When tested on isolated skeletal muscle (chick biventer cervicis, chick embryo muscle in culture, guinea pig hemidiaphragm) and cardiac muscle (guinea pig and cat left atria, cat papillary muscle) preparations, fractions II, III and IV, but not fraction I, caused contracture and depolarization. The cardiotoxin-induced contractions could be prevented by pretreatment with raised concentrations of calcium, but were not influenced by a wide range of pharmacological agents which modify nerve-muscle transmission or muscle contractility. The results suggest that cardiotoxins do not act at a specific step in normal excitation-contraction coupling but directly on cell membranes, where they probably cause the formation of pores which result in depolarization and in the influx of calcium.