Roden D M, Bennett P B, Snyders D J, Balser J R, Hondeghem L M
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Circ Res. 1988 May;62(5):1055-8. doi: 10.1161/01.res.62.5.1055.
A major action of the antiarrhythmic agent quinidine is prolongation of cardiac repolarization. In these experiments, the time-dependent effects of quinidine on the delayed rectifier potassium current, IK, a current contributing to cardiac repolarization, were investigated in acutely disaggregated guinea pig ventricular myocytes using the whole-cell recording configuration of the patch-clamp method. The effect of quinidine on IK was dependent on the duration of depolarization. After long (2,000 msec) pulses, IK was reduced by 30 +/- 27% (SD; n = 8, paired) by 10 microM quinidine; in contrast, after short (100 msec) pulses, the drug decreased IK 65 +/- 35% (p less than 0.05). This effect was found both in paired experiments as well as when quinidine-pretreated cells were compared to non-pretreated cells. Quinidine significantly delayed IK activation (9 +/- 20 msec at baseline vs. 44 +/- 25 msec in drug, p less than 0.05), but did not alter the subsequent time course of activation (time constant 659 +/- 118 msec). These findings are consistent with the hypothesis that quinidine promotes occupancy of a channel state from which opening does not occur.
抗心律失常药物奎尼丁的一个主要作用是延长心脏复极化。在这些实验中，使用膜片钳方法的全细胞记录模式，在急性分离的豚鼠心室肌细胞中研究了奎尼丁对延迟整流钾电流（IK，一种有助于心脏复极化的电流）的时间依赖性影响。奎尼丁对IK的作用取决于去极化的持续时间。在长（2000毫秒）脉冲后，10微摩尔奎尼丁使IK降低了30±27%（标准差；n = 8，配对）；相比之下，在短（100毫秒）脉冲后，该药物使IK降低了65±35%（p < 0.05）。在配对实验以及将用奎尼丁预处理的细胞与未预处理的细胞进行比较时都发现了这种效应。奎尼丁显著延迟了IK的激活（基线时为9±20毫秒，药物作用下为44±25毫秒，p < 0.05），但没有改变随后的激活时间进程（时间常数为659±118毫秒）。这些发现与奎尼丁促进占据一个不会发生开放的通道状态的假设一致。
