OMEGA-AGATOXIN IVA BLOCKS NICOTINIC RECEPTOR CHANNELS IN BOVINE CHROMAFFIN CELLS

We have studied the contribution of P-type voltage-dependent Ca2+ chan nels to both catacholamine (CA) and ATP secretion from bovine chromaff in cells induced by high K+ or nicotine using omega-agatoxin IVA, a se lective blocker of P-type voltage-dependent Ca2+ channels. We found th at 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 acid ATP secr etion were significantly blocked (about 50%) by omega-agatoxin IVA (10 0 nM), In addition, this toxin also reversibly blocked (about 70%) the inward current induced by nicotine in bovine chromaffin cells. The re sults suggest that, besides its known action of blocking P-type voltag e-dependent channels, omega-agatoxin is a potent and reversible blocke r of the nicotinic receptor channel in chromaffin cells, and that this action would explain the blockade of nicotine-induced secretion.