We have studied the contribution of P-type voltage-dependent Ca2+ channels to both catacholamine (CA) and ATP secretion from bovine chromaffin cells induced by high K+ or nicotine using omega-agatoxin IVA, a selective blocker of P-type voltage-dependent Ca2+ channels. We found that high K+ (75 mM) induced the release of about 13% of norepinephrine, 5% epinephrine and 11% ATP, and that omega-agatoxin (100 nM) did not affect this secretion. However, both nicotine-induced CA and ATP secretion were significantly blocked (about 50%) by omega-agatoxin IVA (100 nM). In addition, this toxin also reversibly blocked (about 70%) the inward current induced by nicotine in bovine chromaffin cells. The results suggest that, besides its known action of blocking P-type voltage-dependent channels, omega-agatoxin is a potent and reversible blocker of the nicotinic receptor channel in chromaffin cells, and that this action would explain the blockade of nicotine-induced secretion.

This work was supported, in part, by grants from Fundación Salud 2000, Dirección General de Investigación Cientifica y Técnica, Grant PM92-0112, and the European Economic Community, Grant SC1"-CT91-0709. R.G. was supported by a University of Alicante fellowship, J.M.F. by a CAM fellowship, and V.I. by a Generalitat Valenciana fellowship.