Combined Effects of Acidosis, Hypoxia, and Anesthetics on the K_<ATP> Channels in Isolated Rat Myocytes.

应用膜片钳技术研究了麻醉药对大鼠心室肌细胞ATP敏感性钾通道的影响<ATP>。由于K_通道的激活<ATP>是由细胞内ATP耗竭引起的，我们用DNP（一种线粒体ATP合成的抑制剂）或无ATP溶液模拟缺血。在细胞贴壁和由内向外两种构型中，K_1<ATP>通道活性均被硫代戊醛浓度依赖性地抑制。这些结果表明，硫代戊醛直接抑制钾<ATP>通道。此外，这种阻断是可逆的，因此我们可以观察到通过洗脱硫戊醛而重现通道活性。然后，<ATP>用pH=6.5的酸性电解液代替DNP溶液，研究了硫代戊醛对K通道活性的影响。硫代戊醛也抑制<ATP>酸性溶液中的钾通道。我们还研究了其他麻醉剂与K_通道的相互作用<ATP>，使用与上述相同的方法。挥发性麻醉药（1MAC氟烷、异氟烷和七氟烷）可使钾通道活性降低，<ATP>而异丙酚对钾通道活性无影响。当外推到临床情况时，必须适当谨慎地看待从对照动物实验中获得的结果。本研究结果提示，硫戊醛和挥发性麻醉药可抑制心肌梗塞时钾通道的心肌保护作用<ATP>。

Using patch clamp technique we investigated the effects of anesthetics on the ATP sensitive potassium (K_<ATP>) channels in rat ventricular myocytes. Since the activation of the K_<ATP> channels is caused by intracellular ATP depletion, we used DNP (an inhibitor of mitochondrial ATP synthesis) or ATP-free solution to simulate ischemia. In both cell-attached and inside-out configurations, the K_<ATP>, channel activities were suppressed by thiamylal in a concentration-dependent manner. These data suggest that thiamylal inhibits the K_<ATP> channels directly. Furthermore, this blockade was reversible, thus we could observe the reappearance of the channel activities by washing out thiamylal. Then, we studied the effects of thiamylal on the K_<ATP> channel activities using acidotic bath solution (pH=6.5) instead of DNP solution. Thiamylal also inhibited the K_<ATP> channels in aciotic solution. We also studied the interaction of other anesthetics with the K_<ATP> channels, using the same methods as described above. Volatile anesthetics (1 MAC of halothane, isoflurane and sevoflurane) caused reductions in the activities of the K_<ATP>, channels but propofol did not affect the channel activities. Results obtained from controlled animal experiments must be viewed with appropriate caution when extrapolating to the clinical situation. The results obtained in this study suggest that thiamylal and volatile anesthetics may inhibit the cardioprotective effects of the K_<ATP> channels during myocardial infarction.