Cardioprotective effect of diazoxide is mediated by activation of sarcolemmal but not mitochondrial ATP-sensitive potassium channels in mice
Cardioprotective effect of diazoxide is mediated by activation of sarcolemmal but not mitochondrial ATP-sensitive potassium channels in mice
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DOI：
10.1161/01.cir.0000055187.67365.81
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发表时间：
2003-02-11
期刊：
影响因子：
37.8
通讯作者：
Nakaya, H
中科院分区：
文献类型：
--
作者：
Suzuki, M;Saito, T;Nakaya, H
背景-我们最近证明，肌膜 ATP 敏感钾 (sarcK(ATP)) 通道在 Kir6.2 敲除 (KO) 小鼠的心肌缺血/再灌注损伤中发挥关键作用。在本研究中，我们评估了二氮嗪（一种线粒体 ATP 敏感钾 (mitoK(ATP)) 通道开放剂）对 sarcK(ATP) 通道缺陷小鼠缺血引起的心肌顿抑的影响。方法和结果 - 对野生型 (WT) 和 KO 小鼠进行 Langendorff 灌注心脏进行全面缺血/再灌注。二氮嗪改善了 WT 心脏的收缩功能恢复，但没有改善 KO 心脏的收缩功能。使用 HMR1098（一种 sarcK(ATP) 通道阻滞剂）而非 5-羟基癸酸（一种 mitoK(ATP) 通道阻滞剂）治疗可消除二氮嗪对 WT 心脏的心脏保护作用。在冠状动脉灌注的 WT 心室肌制剂中，二氮嗪存在时会加速缺血期间的动作电位缩短。结论：二氮嗪通过激活 sarcK(ATP) 通道来增强缺血期间的动作电位缩短，并为小鼠心脏提供心脏保护。
Background-We recently demonstrated that the sarcolemmal ATP-sensitive potassium (sarcK(ATP)) channel plays a key role in cardioprotection against ischemia/reperfusion injuries in Kir6.2-knockout (KO) mice. In the present study, we evaluated the effects of diazoxide, a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel opener, on ischemia-induced myocardial stunning in sarcK(ATP) channel-deficient mice.Methods and Results-Langendorff-perfused hearts of wild-type (WT) and KO mice were subjected to global ischemia/reperfusion. Diazoxide improved the recovery of contractile function in WT hearts but not in KO hearts. Treatment with HMR1098 (a sarcK(ATP) channel blocker) but not 5-hydroxydecanoate (a mitoK(ATP) channel blocker) abolished the cardioprotective effect of diazoxide in WT hearts. In coronary-perfused WT ventricular muscle preparations, action potential shortening during ischemia was accelerated in the presence of diazoxide.Conclusions-Diazoxide enhances action potential shortening during ischemia by activating sarcK(ATP) channels and provides cardioprotection in mouse hearts.