Effects of Divalent Cations on Snake Venom Cardiotoxin-Induced Hemolysis and 3H-Deoxyglucose-6-Phosphate Release from Human Red Blood Cells

摘要

At a low concentration of Naja naja kaouthia cardiotoxin (3 microns) Ca(2+), Sr(2+), and Ba(2+) (2 nM), had little to no effect on Tritium -deoxyglucose-6-phosphate (3H-dGlu-6-p) or hemoglobin release. At higher concentrations of N. n. kaouthia cardiotoxin > or = 10 microns, Ca (2+) (2 mM), but not Sr (2+) or Ba (2+), significantly enhanced 3H-dGlu-6-p and hemoglobin release. Mn(2+) (2 mM) almost completely inhibited 3H-dGlu-6-p release and hemolysis at both the 3 microns and 10 microns concentrations of cardiotoxin. At a fixed concentration of N. n. kauthia cardiotoxin (3 microns), Ca (2+) at low concentrations (0.5 mM) enhanced 3H-dGlu-6-p and hemoglobin release, but at higher concentrations caused a dose-dependent inhibition of cardiotoxin action. The cardiotoxin from N. n. kaouthia venom (3 microns) induced 3-H-dGlu-6-P release and hemolysis release with similar time courses and to similar extents. 3H-dGlu-6-p release induced by cardiotoxin was greatly enhanced as the pH of the medium was increased from 7.0 to 8.5 Similarities between 3H-dGlu-6-p and hemoglobin release do not support opening of pores in the plasmalemma of all red blood cells as the mode of action of cardiotoxins, but suggest that complete lysis of a subpopulation of cells occurs. Cardiotoxins have two components of lysis, only one of which is Ca(2+)-dependent. The Ca(2+)-dependent lysis is only evident at higher cardiotoxin concentrations. Mn(2+) is an effective antagonist of cardiotoxin action.