Interaction of SK sub(Ca) channels and L-type Ca super(2+) channels in catecholamine secretion in the rat adrenal gland

We elucidated the interaction of small-conductance Ca super(2+)-activated K super(+) (SK sub(Ca)) channels and L-type Ca super(2+) channels in muscarinic receptor-mediated control of catecholamine secretion in the isolated perfused rat adrenal gland. The muscarinic agonist methacholine (10-300 mu M) produced concentration-dependent increases in adrenal output of epinephrine and norepinephrine. The SK sub(Ca) channel blocker apamin (1 mu M) 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 Ca super(2+) channel blocker nifedipine (3 mu M) or Ca super(2+)-free solution. Nifedipine did not affect the methacholine-induced catecholamine responses, but it inhibited the responses during treatment with apamin. The L-type Ca super(2+) channel activator Bay k 8644 (1 mu M) 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 SK sub(Ca) channels are activated by muscarinic receptor stimulation, which inhibits the opening of L-type Ca super(2+) channels and thereby attenuates adrenal catecholamine secretion.