LARGE-AND SMALL-CONDUCTANCE CA2-ACTIVATED K+ CHANNELS - THEIR ROLE INTHE NICOTINIC RECEPTOR-MEDIATED CATECHOLAMINE SECRETION IN BOVINE ADRENAL-MEDULLA()

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