Activation of mitochondrial ATP-dependent potassium channels by nitric oxide
Activation of mitochondrial ATP-dependent potassium channels by nitric oxide
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DOI：
10.1161/01.cir.101.4.439
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发表时间：
2000-02-01
期刊：
影响因子：
37.8
通讯作者：
Marbán, E
中科院分区：
文献类型：
--
作者：
Sasaki, N;Sato, T;Marbán, E
背景-一氧化氮(NO)被认为是“第二窗”缺血预适应的介质，线粒体ATP依赖性钾通道(mitoK(ATP))可能是其影响因素。方法与结果：我们测定了线粒体氧化还原电位作为心肌细胞线粒体线粒体K-ATP通道开放的指标，NO供体S-亚硝基-N-乙酰-DL-青霉胺(SNAP，0.1~1 mmol/L)以剂量依赖的方式氧化线粒体基质而不激活肌膜K-ATP通道。SNAP诱导的线粒体氧化可被选择性的丝裂原激活剂通道阻断剂5-羟基癸酸和NO清除剂2-(4-carboxyphenyl)-4，4‘，5，5’-tetramethylimidazole-1-oxyl-3-Oxid阻断，可通过黄素蛋白荧光的光电倍增管记录或共聚焦成像检测到。当两种试剂一起使用时，Snap也增强了二氮卓的氧化作用。暴露于1 mmol/L的8BrcGMP不能模拟SNAP的作用。结论：NO可直接激活线粒体K通道，并增强二氮嗪对该通道的开放作用。这些结果在NO诱导的心肌保护和线粒体K(ATP)通道之间提供了新的机制联系。
Background-Nitric oxide (NO) has been implicated as a mediator of "second-window" ischemic preconditioning, and mitochondrial ATP-dependent K+ (mitoK(ATP)) channels are the likely effecters. The links between NO and mitoK(ATP) channels are unknown.Methods and Results-We measured mitochondrial redox potential as an index of mitoK(ATP) channel opening in rabbit ventricular myocytes, The NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP, 0.1 to 1 mmol/L) oxidized the mitochondrial matrix dose-dependently without activating sarcolemmal K-ATP channels. SNAP-induced oxidation was blocked by the selective mitoK(ATP) channel blocker 5-hydroxydecanoate and by the NO scavenger 2-(4-carboxyphenyl)-4,4',5,5'-tetramethylimidazole-1 -oxyl-3-oxide, SNAP-induced mitochondrial oxidation was detectable either by photomultiplier tube recordings of flavoprotein fluorescence or by confocal imaging. SNAP also enhanced the oxidative effects of diazoxide when both agents were applied together. Exposure to 1 mmol/L 8Br-cGMP failed to mimic the effects of SNAP.Conclusions-NO directly activates mitoK(ATP) channels and potentiates the ability of diazoxide to open these channels. These results provide novel mechanistic Links between NO-induced cardioprotection and mitoK(ATP) channels.