Large- and small-conductance Ca²⁺-activated K⁺ channels: their role in the nicotinic receptor-mediated catecholamine secretion in bovine adrenal medulla

Abstract

In cultured bovine adrenal chromaffln cells, charybdotoxin and iberiotoxin (inhibitors of the large-conductance Ca²⁺-activated K⁺ channel) as well as apamin (an inhibitor of the small-conductance Ca²⁺-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 Ca²⁺-activated K⁺ channels, and that the blockade of these Ca²⁺-activated K⁺ channels results in gating of voltage-dependent Ca²⁺ channels and thereby augments catecholamine secretion from bovine adrenal chromaffln cells.