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

酸中毒、缺氧和麻醉对离体大鼠肌细胞 K_<ATP> 通道的综合影响。

• 批准号: 09671568
• 负责人: OSHITA Shuzo
• 金额: $ 2.11万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671568/
• 关键词: ventricular myocytes; ATP sensitive potassium channel; anesthetics; ATP感受性Kチャンネル

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.

应用膜片钳技术，观察麻醉药对大鼠心室肌细胞ATP敏感性钾通道的影响。由于K&lt；ATP&gt；通道的激活是由细胞内ATP耗竭引起的，所以我们使用DNP(一种线粒体ATP合成的抑制剂)或无ATP的溶液来模拟缺血。在细胞连接和由内向外的两种构型中，硫代戊醛均以浓度依赖的方式抑制通道活性。这些数据表明，硫柳汞直接抑制K_&lt；ATP&gt；通道。此外，这种阻断是可逆的，因此我们可以通过清洗硫代戊醛来观察到通道活动的再现。然后，我们用酸性浴液(pH=6.5)代替DNP溶液，研究了硫代戊醛对K&lt；ATP&Gt；通道活性的影响。在酸性溶液中，硫代戊醛对K&lt；ATP和Gt；通道也有抑制作用。我们还用与上述相同的方法研究了其他麻醉剂与K_&lt；ATP&gt；通道的相互作用。挥发性麻醉剂(氟烷、异氟醚和七氟醚各1 MAC)引起K_1通道活动降低，而异丙酚对通道活动无影响。从对照动物实验获得的结果在推断临床情况时必须适当谨慎地看待。本研究结果提示，硫代戊醛和挥发性麻醉药可抑制心肌梗死时K&lt；ATP&gt；通道的心脏保护作用。