Effects of omega-conotoxin MVIIC on veratridine-induced cytotoxicity and cytosolic Ca2+ oscillations

External Ca2+ entry through various Ca2+-channel subtypes is responsible for the large oscillations of the cytosolic Ca2+ concentrations, [Ca2+](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+ channels, or by furnidipine of L-type Ca2+ channels did not afford cytoprotection. 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 the cytoprotecting effects of MVIIC. MVIIC but not furnidipine, markedly reduced the oscillations of [Ca2+](i) induced by veratridine in single fura-2-loaded chromaffin cells. The results suggest that Ca2+ entry through any of the different Ca2+ channel subtypes present in bovine chromaffin cells might be cytotoxic. They also support two ideas: (i) that 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 Ca2+ channel blockers may provide greater cytoprotection than single compounds.