Findlay I, Deroubaix E, Guiraudou P, Coraboeuf E
Laboratoire de Physiologie Comparée, Université de Paris XI, Orsay, France.
Am J Physiol. 1989 Nov;257(5 Pt 2):H1551-9. doi: 10.1152/ajpheart.1989.257.5.H1551.
A cromakalim analogue, SR 44866, is shown to open ATP-sensitive K+ channels in ventricular myocytes. The channels opened by SR 44866 were closed by internal ATP and had the same current-voltage relationship as ATP-sensitive K+ channels; channels closed by ATP could be opened by SR 44866. SR 44866 was effective when applied to either side of excised membrane patches and when included in the pipette during cell-attached membrane recordings. SR 44866 also opened channels in cell-attached membrane patches when it was applied to the cell membrane outside of the pipette. The current evoked by SR 44866 in whole cell recordings was inhibited by tolbutamide. SR 44866 reduced the duration of action potentials and the amplitude and duration of evoked muscle contractions in guinea pig papillary muscle, with dissociation constants of 6.8 microM at 24 degrees C and 1.9 microM at 34 degrees C and Hill coefficients of 1.72 and 1.71, respectively. We conclude that the opening of ATP-sensitive K+ channels has profound inhibitory effects on the electrical and mechanical activity of cardiac muscle.
一种克罗卡林类似物SR 44866，被证明可在心室肌细胞中打开ATP敏感性钾通道。由SR 44866打开的通道可被胞内ATP关闭，且其电流-电压关系与ATP敏感性钾通道相同；被ATP关闭的通道可被SR 44866打开。当将SR 44866应用于切除膜片的任一侧以及在细胞贴附式膜片记录期间包含在微管中时，它都是有效的。当将SR 44866应用于微管外部的细胞膜时，它也能打开细胞贴附式膜片中的通道。在全细胞记录中，SR 44866诱发的电流被甲苯磺丁脲抑制。SR 44866缩短了豚鼠乳头肌动作电位的持续时间以及诱发肌肉收缩的幅度和持续时间，在24℃时解离常数为6.8微摩尔，在34℃时为1.9微摩尔，希尔系数分别为1.72和1.71。我们得出结论，ATP敏感性钾通道的开放对心肌的电活动和机械活动具有深远的抑制作用。
