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

我们利用膜片钳技术研究了异丙酚对大鼠心室肌细胞肌膜三磷酸腺苷敏感钾（K_<ATP>）通道活性的影响，以及K_<ATP>通道在缺血诱导预处理（IPC）的保护作用中的作用。异丙酚以浓度依赖的方式抑制K_<ATP>通道的活性，无论是在内向外的构型还是在细胞附着构型中。这些数据表明，异丙酚以膜分隔的方式抑制K_<ATP>通道活性，而不是通过细胞质第二信使。然后，我们评估了肌层K_<ATP>通道活性对缺血预处理的影响。短暂的缺血发作可使心脏免受长时间的缺血损伤，这被称为IPC。大量研究支持三磷酸腺苷敏感钾（K_<ATP>）通道可能在这一过程中起末端效应。非预处理组（对照组）连续缺血15分钟，预处理组（IPC组）缺血5分钟，再灌注5分钟，最后缺血5分钟。为了模拟缺血，我们使用2,4-二硝基苯酚（DNP），一种线粒体ATP合成抑制剂，在细胞附着的结构中，并以低ATP的Tyroide溶液在内向外的结构中灌注。在细胞连接构型中，IPC组的K_<ATP>通道开放概率较对照组显著增加。然而，在内向外结构中，对照组和IPC组之间K_<ATP>通道的开放概率没有显著差异。这些结果表明，IPC的心脏保护作用是由于增加了K_<ATP>通道的开放概率，而这些特性可能是通过细胞质第二信使介导的。

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.