Koumi S, Sato R, Hayakawa H, Okumura H
First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
J Mol Cell Cardiol. 1991 Apr;23(4):427-38. doi: 10.1016/0022-2828(91)90167-k.
To determine if the fast sodium current inactivation process is necessary for sodium current (INa) blockade by quinidine, we studied the effects of quinidine on INa in guinea-pig ventricular myocytes treated with chloramine-T, which removes the fast inactivation process of INa. Following exposure to chloramine-T (2 mM), INa amplitude was reduced at all voltages and INa decay was irreversibly prevented. Quinidine (10 microM) produced resting block of INa of 36 +/- 2% (n = 5) at the peak potential of -30 mV in chloramine-T treated myocytes. Quinidine decreased INa in a dose-dependent manner. The half-blocking concentration (KD) was 1.9 +/- 0.2 x 10(-5) M (n = 4). The steady-state inactivation curve (hx) was shifted in the negative potential direction (-5.2 +/- 0.4 mV, n = 4). Even after removal of the fast inactivation process of INa, use-dependent block was observed in the presence of quinidine when various depolarizing pulse durations (5 ms approximately 200 ms) were applied repetitively at intervals of 300 ms approximately 2 s. Longer depolarizing pulses and higher frequency pulse trains produced greater use-dependent block. Use-dependent block was also enhanced at more positive holding potentials. These results suggest that quinidine produces both resting block and use-dependent block of sodium channels in the absence of the fast INa inactivation process.
为了确定快速钠电流失活过程对于奎尼丁阻断钠电流（INa）是否必要，我们研究了奎尼丁对用氯胺 - T处理的豚鼠心室肌细胞中INa的影响，氯胺 - T可消除INa的快速失活过程。暴露于氯胺 - T（2 mM）后，所有电压下INa幅度均降低，并且INa衰减被不可逆地阻止。在氯胺 - T处理的心肌细胞中，在 - 30 mV的峰值电位下，奎尼丁（10 microM）产生的INa静息阻断为36±2%（n = 5）。奎尼丁以剂量依赖性方式降低INa。半阻断浓度（KD）为1.9±0.2×10（ - 5）M（n = 4）。稳态失活曲线（hx）向负电位方向移动（ - 5.2±0.4 mV，n = 4）。即使在消除INa的快速失活过程后，当以300 ms至2 s的间隔重复施加各种去极化脉冲持续时间（5 ms至200 ms）时，在奎尼丁存在的情况下仍观察到使用依赖性阻断。更长的去极化脉冲和更高频率的脉冲序列产生更大的使用依赖性阻断。在更正的钳制电位下，使用依赖性阻断也增强。这些结果表明，在不存在快速INa失活过程的情况下，奎尼丁会产生钠通道的静息阻断和使用依赖性阻断。
