Effects of omega-conotoxin MVIIC on veratridine-induced cytotoxicity and cytosolic Ca(2+) oscillations.
External Ca(2+) entry through various Ca(2+)-channel subtypes is responsible for the large oscillations of the cytosolic Ca(2+) concentrations, [Ca(2+)](i), and cell death induced by veratridine in primary cultures of bovine chromaffin cells. Blockade by omega-conotoxin GVIA (GVIA) of N-type Ca(2+) channels, by omega-agatoxin IVA (IVA) of P-type Ca(2+) channels, or by furnidipine of L-type Ca(2+) channels did not afford cytoprotection. However, (omega-conotoxin MVIIC (MVIIC), a wide-spectrum blocker of N-, P- and Q-type Ca(2+) channels greatly protected the cells against the cytotoxic effects of veratridine. Furnidipine further enhanced the cytoprotecting effects of MVIIC. MVIIC but not furuidipine, markedly reduced the oscillations of [Ca(2+)](i) induced by veratridine in single fura-2-loaded chromaffin cells. The results suggest that Ca(2+) entry through any of the different Ca(2+) channel subtypes present in bovine chromaffin cells might be cytotoxic. They also support two ideas: (i) that wide-spectrum neuronal Ca(2+) channel blockers (i.e. MVIIC) might be better cytoprotecting agents than more specific neuronal Ca(2+) channel blockers (i.e., GVIA, IVA, furnidipine); and (ii) that combined Ca(2+) channel blockers may provide greater cytoprotection than single compounds.
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Departamento de Farmacología, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain.
de la Fuente
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García
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D000311:Adrenal Glands / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010455:Peptides / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D002395:Catecholamines; D004095:Dihydropyridines; D010455:Peptides; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D014701:Veratridine; C082391:furnidipine; D002118:Calcium