| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Research Abstract |
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.
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