The role of K_<ATP> channel activities on the ischemic preconditioning and the influence of anesthetics on K_<ATP> channel activities.

K_<ATP>通道活性对缺血预处理的作用及麻醉药对K_<ATP>通道活性的影响。

• 批准号: 11671501
• 负责人: OSHITA Shuzo
• 金额: $ 2.3万
• 依托单位: Tokushima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671501/
• 关键词: Ischemic preconditioning; Cardioprotection; Patch-clamp technique; K_<ATP> channel; Intravenous anesthetic; Propofol; 麻酔薬

We examine the effects of propofol on the sarcolemmal adenosine triphoshate-sensitive potassium (K_<ATP>) channel activities and the role of K_<ATP> channels on the carioprotective effects of ischemia-induced preconditioning (IPC) using patch-clamp techniques in rat ventricular myocytes. Propofol inhibited K_<ATP> channel activities in a concentration-dependent manner both in inside-out and in cell-attached configurations. These data suggest that propofol inhibits K_<ATP> channel activities in a membrane-delimited manner rather than through a cytosolic second messenger.Then, we evaluated the effects of sarcolemmal K_<ATP> channel activities on the ischemic preconditioning. A brief episode of iscemia render the cardioprotection against a prolonged ischemic damages, which is known as IPC.Numerous of studies support that the adenosine triphoshate-sensitive potassium (K_<ATP>) channels may serve as the end effector in these prosess. Nonpreconditioned group (control group) received a continuos 15 minutes ischemia, whereas preconditioned group (IPC group) subjected to 5 minutes ischemia, 5 minutes reperfusion, and finally 5 minutes ischemia. To simulate ischmia we used 2,4-dinitrophenol (DNP), an inhibitor of mitochondrial ATP synthesis, in cell-attached configurations and perfused with low-ATP Tyroide's solution in inside-out configurations. In the cell-attached configurations, the open probability of the K_<ATP> channels in the IPC group was significantly increased compared to that of the control group. In the inside-out configuration, however, there were no significant differences in open probability of the K_<ATP> channels between control and IPC groups. These results indicate that cardioprotective effects of IPC are due to increased open probability of K_<ATP> channels, and these characteristics of sarcolemmal K_<ATP> channels might be mediated through cytosolic second messengers.

采用膜片钳技术观察异丙酚对大鼠心室肌细胞膜ATP敏感性钾通道（K_2）活性的影响<ATP>，并探讨K_2通道<ATP>在缺血预处理（IPC）心肌保护中的作用。异丙酚抑制K_<ATP>（1+）通道活动，并呈浓度依赖性。这些结果表明，异丙酚对心肌细胞膜钾<ATP>通道活性的抑制作用是以膜为界的，而不是通过胞浆的第二信使<ATP>。短暂的缺血可使心肌免受长期缺血性损伤，即IPC，大量研究表明腺苷三磷酸敏感性钾通道（adenosinetriphosate-sensitive potassium，<ATP>K_2）可能是这一过程的终末效应器。非预处理组（对照组）连续缺血15 min，预处理组（IPC组）缺血5 min，再灌注5 min，最后缺血5 min。为了模拟缺血，我们使用2，4-二硝基苯酚（DNP），一种线粒体ATP合成的抑制剂，在细胞附着配置和灌注低ATP Tyroide的溶液在由内而外的配置。在细胞贴附构型中，IPC组的K通道开放概率<ATP>较对照组显著增加。而在由内向外构型中，对照组和IPC组的钾通道开放概率无显著差异<ATP>。这些结果提示IPC的心肌保护作用是通过增加心肌细胞膜钾通道开放概率<ATP>而实现的，而心肌细胞膜钾通道的开放<ATP>可能是通过胞浆第二信使介导的。