Van Bogaert P P, Goethals M
Department of Biochemistry, Physiology & Genetics, University of Antwerp (RUCA), Belgium.
Eur J Pharmacol. 1992 Dec 8;229(1):55-62. doi: 10.1016/0014-2999(92)90285-c.
UL-FS 49 (Zatebradine) and its quaternary derivative, UL-AH 99, were injected by iontophoresis in shortened sheep cardiac Purkinje fibres. The i(f) pacemaker current changes were analyzed using the two-microelectrode voltage-clamp technique. Injection of either drug resulted in a decrease of the maximal diastolic depolarization rate as a consequence of a reduction in i(f) amplitude, with no changes in the kinetics of this current or in voltage dependence. The i(f) blockade was proportional to the total charge injected. After drug iontophoresis under conditions where no i(f) current was activated, an exponential use-dependent decline in i(f) tail current was observed during the application of a voltage-clamp pulse train activating i(f). A slow recovery from blockade, measured after prolonged hyperpolarizations, followed exponential kinetics. Recovery rate and extent of steady state recovery increased with more negative potentials. This suggests that bradycardiac agents interact with the i(f) channel in cationic form from the inside of the cell.
将UL-FS 49（扎替丁）及其季铵衍生物UL-AH 99通过离子电渗疗法注入缩短的绵羊心脏浦肯野纤维中。使用双微电极电压钳技术分析I(f)起搏电流的变化。注射任何一种药物都会导致最大舒张期去极化速率降低，这是由于I(f)幅度降低所致，而该电流的动力学或电压依赖性没有变化。I(f)阻断与注入的总电荷量成正比。在未激活I(f)电流的条件下进行药物离子电渗后，在施加激活I(f)的电压钳脉冲序列期间，观察到I(f)尾电流呈指数性使用依赖性下降。在长时间超极化后测量的阻断缓慢恢复遵循指数动力学。恢复速率和稳态恢复程度随着电位更负而增加。这表明心动过缓药物以阳离子形式从细胞内部与I(f)通道相互作用。
