Large- and small-conductance Ca(2+)-activated K+ channels: their role in the nicotinic receptor-mediated catecholamine secretion in bovine adrenal medulla.

In cultured bovine adrenal chromaffin cells, charybdotoxin and iberiotoxin (inhibitors of the large-conductance Ca(2+)-activated K+ channel) as well as apamin (an inhibitor of the small-conductance Ca(2+)-activated K+ channel), at 1-100 nM, suppressed carbachol-induced 86RB+ efflux, augmented carbachol-induced 45Ca2+ influx via voltage-dependent Ca2+ channels and catecholamine secretion and had no effect on carbachol-induced 22Na+ influx via nicotinic receptors, a prerequisite for Ca2+ channel activation by carbachol. 45Ca2+ influx caused by high K+ (a direct activation of voltage-dependent Ca2+ channels) was also enhanced by these K+ channel inhibitors, with the concentration-response curves being similar to those for carbachol-induced 45Ca2+ influx. Dendrotoxin and mast cell degranulating peptide (inhibitors of voltage-dependent K+ channels), on the other hand, did not alter carbachol-induced 86Rb+ efflux or 45Ca2+ influx. These results suggest that the stimulation of nicotinic receptors eventually opens large- and small-conductance Ca(2+)-activated K+ channels, and that the blockade of these Ca(2+)-activated K+ channels results in gating of voltage-dependent Ca2+ channels and thereby augments catecholamine secretion from bovine adrenal chromaffin cells.