Cobra venom cardiotoxin induces aggregation of washed rat platelets: dual effects of Ca2+

The effects of cardiotoxin isolated and purified from the venom of Naja naja atra on the platelet aggregation were investigated using washed rat platelets prepared chromatographically. In the presence of 1 mM Ca2+, cardiotoxin concentration-dependently induced aggregation of platelets. While extracellular Ca2+ was necessary for the induction of aggregation by cardiotoxin, high concentration of Ca2+ (e.g., 5 mM) prevented cardiotoxin-induced aggregation. Cardiotoxin-induced platelet aggregation was also blocked by 1 mM Ni2+ but not by 100 microM indomethacin or 1 microM nifedipine, indicating that cardiotoxin-induced platelet aggregation involved Ca(2+)-entry pathway other than L-type Ca2+ channels. High concentration of Ca2+ may prevent cardiotoxin-induced aggregation by competing with cardiotoxin for binding site on the platelet membranes.