Blockade of Adenosine Triphosphate–sensitive Potassium Channels by Thiamylal in Rat Ventricular Myocytes
Blockade of Adenosine Triphosphate–sensitive Potassium Channels by Thiamylal in Rat Ventricular Myocytes
复制标题
硫淀粉醛阻断大鼠心室肌细胞中的三磷酸腺苷敏感钾通道
作者：
Y. Tsutsumi;S. Oshita;H. Kitahata;Y. Kuroda;T. Kawano;Y. Nakaya
背景：三磷酸腺苷（ATP）敏感钾（KATP）通道在缺血和再灌注过程中保护肌细胞。本研究探讨了硫氨酰对离体大鼠心室肌细胞模拟缺血时KATP通道活性的影响。方法：用乙醚麻醉雄性Wistar大鼠。单个静止的心室肌细胞被酶分散。膜片钳技术记录膜电流。在细胞连接的结构中，在2,4-二硝基苯酚激活这些通道之前和期间以及施用25、50和100 mg/l硫胺醛后，评估KATP通道电流。打开概率由电流振幅直方图确定。在内外构型下，得到了硫胺醛（50 mg/l）应用前后的电流-电压关系。结果：在细胞附着构型中，2,4-二硝基苯酚引起通道频繁打开。2,4-二硝基酚诱导的通道活性被格列本脲显著降低，表明所研究的通道是KATP通道。硫胺醛以浓度依赖性的方式降低KATP通道的打开概率。由于缺乏ATP， KATP通道可以在内向外的配置中被激活。硫胺醛抑制KATP通道活性，但不改变单通道电导。结论：本研究结果表明，硫氨酰可抑制细胞贴附斑块和内外斑块的KATP通道活性，提示该药物可直接作用于这些通道。
Background: The adenosine triphosphate (ATP)–sensitive potassium (KATP) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of thiamylal on the activities of KATP channels in isolated rat ventricular myocytes during simulated ischemia. Methods: Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, KATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l thiamylal. The open probability was determined from current–amplitude histograms. In the inside-out configuration, the current–voltage relation was obtained before and after the application of thiamylal (50 mg/l). Results: In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol–induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were KATP channels. Open probability of KATP channels was reduced by thiamylal in a concentration-dependent manner. KATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited KATP channel activity without changing the single-channel conductance. Conclusions: The results obtained in this study indicate that thiamylal inhibits KATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.
影响因子：
37.8
作者：
Liu, YG;Sato, T;Marban, E
通讯作者：
Marban, E
影响因子：
56.9
作者：
J. Weiss;S. Lamp
通讯作者：
J. Weiss;S. Lamp