EFFECTS OF OMEGA-CONOTOXIN MVIIC ON VERATRIDINE-INDUCED CYTOTOXICITY AND CYTOSOLIC CA2+ OSCILLATIONS

External Ca2+ entry through various Ca2+-channel subtypes is responsib le for the large oscillations of the cytosolic Ca2+ concentrations, [C a2+](i), and cell death induced by veratridine in primary cultures of bovine chromaffin cells. Blockade by omega-conotoxin GVIA (GVIA) of N- type Ca2+ channels, by omega-agatoxin IVA (IVA) of P-type Ca2+ channel s, or by furnidipine of L-type Ca2+ channels did not afford cytoprotec tion. However, omega-conotoxin MVIIC (MVIIC), a wide-spectrum blocker of N-, P- and Q-type Ca2+ channels greatly protected the cells against the cytotoxic effects of veratridine. Furnidipine further enhanced th e cytoprotecting effects of MVIIC. MVIIC but not furnidipine, markedly reduced the oscillations of [Ca2+](i) induced by veratridine in singl e fura-2-loaded chromaffin cells. The results suggest that Ca2+ entry through any of the different Ca2+ channel subtypes present in bovine c hromaffin cells might be cytotoxic. They also support two ideas: (i) t hat wide-spectrum neuronal Ca2+ channel blockers (i.e. MVIIC) might be better cytoprotecting agents than more specific neuronal Ca2+ channel blockers (i.e., GVIA, IVA, furnidipine); and (ii) that combined Ca2channel blockers may provide greater cytoprotection than single compou nds.