线粒体ATP敏感性钾通道激活延缓大鼠心肌缺血引起的细胞间电脱耦联

• 作者: 吴迅冬 夏强 沈岳良 陈莹莹
• 来源期刊: 中国药理学报（英文版）
• 学科: 医学
• 关键词: heart mitochondria potassium channels adenosine triphosphate ischemic preconditioning uncou-pling
• 年，卷（期）: 2004,（1）
• 所属期刊栏目: 研究原著
• 页码范围: 22-28
• 页数: 7页
• 分类号: R54
• 语种: 英文

摘要

AIM: To test the hypothesis that cellular uncoupling induced by myocardial ischemia is mediated by activation of mitochondrial ATP-sensitive potassium channels (mitoKATP). METHODS: Rat hearts were perfused on a Langendorff apparatus and subjected to 40-min ischemia followed by 30-min reperfusion (I/R). Changes in cellular coupling were monitored by measuring whole-tissue resistance. RESULTS: (1) In hearts subjected to I/R, the onset of uncoupling started at (13.3±1.0) min of ischemia; (2) Ischemic preconditioning (IPC) delayed the onset of uncoupling until (22.7± 1.3) min. Blocking mitoKATP channels with 5-hydroxydecanoate (5-HD) before the IPC abolished the uncoupling delay [(12.6+1.6) min]; (3) Calcium preconditioning (CPC) had the same effect as IPC. And this effect was reversed by blocking the mitoKATP channel again. In the CPC group the onset of uncoupling occurred after (20.6±1.3) min, and this was canceled by 5-HD [(13.6±0.8) min]; (4) In hearts pretreated with the specific mitoKATP channel opener diazoxide before sustained ischemia, the onset was delayed to (18.4+ 1.4) min; (5) 5-HD canceled the protective effects of diazoxide (12.6±1.0) min; and both the L-type Ca2+ channel inhibitor verapamil and the free radical scavenger N-(2-mercaptopropionyl)glycine, reduced the extended onset time induced by diazoxide [to (13.3± 1.8) min and (13.4±2.1) min, respectively]. CONCLUSION: IPC and CPC delay the onset of cellular uncoupling induced by acute ischemia in rat heart, and the underlying mechanism involves activation of the mitoKATP channels.