Interaction of SKCachannels and L-type Ca2+channels in catecholamine secretion in the rat adrenal gland

We elucidated the interaction of small-conductance Ca2+-activated K+(SKCa) channels and L-type Ca2+channels in muscarinic receptor-mediated control of catecholamine secretion in the isolated perfused rat adrenal gland. The muscarinic agonist methacholine (10–300 μM) produced concentration-dependent increases in adrenal output of epinephrine and norepinephrine. The SKCachannel blocker apamin (1 μM) enhanced the methacholine-induced catecholamine responses. The facilitatory effect of apamin on the methacholine-induced catecholamine responses was not observed during treatment with the L-type Ca2+channel blocker nifedipine (3 μM) or Ca2+-free solution. Nifedipine did not affect the methacholine-induced catecholamine responses, but it inhibited the responses during treatment with apamin. The L-type Ca2+channel activator Bay k 8644 (1 μM) enhanced the methacholine-induced catecholamine responses, whereas the enhancement of the methacholine-induced epinephrine and norepinephrine responses were prevented and attenuated by apamin, respectively. These results suggest that SKCachannels are activated by muscarinic receptor stimulation, which inhibits the opening of L-type Ca2+channels and thereby attenuates adrenal catecholamine secretion.