Nagayama T, Fukushima Y, Hikichi H, Yoshida M, Suzuki-Kusaba M, Hisa H, Kimura T, Satoh S
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1731-6. doi: 10.1152/ajpregu.2000.279.5.R1731.
We elucidated the interaction of small-conductance Ca(2+)-activated K(+) (SK(Ca)) channels and L-type Ca(2+) channels in muscarinic receptor-mediated control of catecholamine secretion in the isolated perfused rat adrenal gland. The muscarinic agonist methacholine (10-300 microM) produced concentration-dependent increases in adrenal output of epinephrine and norepinephrine. The SK(Ca) channel blocker apamin (1 microM) 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(2+) channel blocker nifedipine (3 microM) or Ca(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(2+) channel activator Bay k 8644 (1 microM) 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(Ca) channels are activated by muscarinic receptor stimulation, which inhibits the opening of L-type Ca(2+) channels and thereby attenuates adrenal catecholamine secretion.
我们阐明了小电导钙激活钾（SK(Ca)）通道与L型钙通道在毒蕈碱受体介导的对离体灌注大鼠肾上腺儿茶酚胺分泌的控制中的相互作用。毒蕈碱激动剂乙酰甲胆碱（10 - 300微摩尔）使肾上腺素和去甲肾上腺素的肾上腺输出呈浓度依赖性增加。SK(Ca)通道阻滞剂蜂毒明肽（1微摩尔）增强了乙酰甲胆碱诱导的儿茶酚胺反应。在用L型钙通道阻滞剂硝苯地平（3微摩尔）或无钙溶液处理期间，未观察到蜂毒明肽对乙酰甲胆碱诱导的儿茶酚胺反应的促进作用。硝苯地平不影响乙酰甲胆碱诱导的儿茶酚胺反应，但它在蜂毒明肽处理期间抑制了这些反应。L型钙通道激活剂Bay k 8644（1微摩尔）增强了乙酰甲胆碱诱导的儿茶酚胺反应，而蜂毒明肽分别阻止和减弱了乙酰甲胆碱诱导的肾上腺素和去甲肾上腺素反应的增强。这些结果表明，毒蕈碱受体刺激激活了SK(Ca)通道，这抑制了L型钙通道的开放，从而减弱了肾上腺儿茶酚胺的分泌。
