Effects of different antagonists on depolarization of cultured chick myotubes by cobra venom cardiotoxins and Pyrularia thionin from the plant Pyrularia pubera.

Cardiotoxins (3.12 and 3.12.1) purified from cobra venom (Naja naja siamensis) are basic single-chain polypeptides of about 60 residues. Although they depolarize nerve and muscle cells and have cytolytic effects, their mechanism of action is still unknown. Pyrularia thionin (P-thionin) isolated from nuts of the parasitic plant Pyrularia pubera is a strongly basic, single-chain polypeptide containing 47 residues. It is known to be haemolytic and cytotoxic, and to depolarize muscle cells, but its mechanism of action is unclear. The present studies explored the possible similarities between P-thionin and cobra venom cardiotoxins by comparing their effects on depolarization of cultured chick skeletal muscle cells in the presence and absence of possible antagonists. Cardiotoxins and P-thionin depolarized cultured chick skeletal muscle cells, but with P-thionin showing a steeper concentration-dependence. Ca2+ was more effective at reducing cardiotoxin action than P-thionin, while the Ca(2+)-channel blockers Ni2+ (100 microM) and verapamil (100 microM) had no blocking effects on the toxins. Ca2+ may block the binding of both toxins. Indomethacin (100 microM, an inhibitor of cyclooxygenase), quinacrine and dexamethasone (100 microM, inhibitors of phospholipase A2) did not block the effects of the toxins, implying that the actions on cultured chick skeletal muscle cells are not due to activation of endogenous phospholipase A2.