Gross G J, Castle N A
Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.
J Mol Cell Cardiol. 1998 Apr;30(4):783-93. doi: 10.1006/jmcc.1998.0643.
This study was aimed at defining cellular electropharmacologic effects of propafenone on repolarizing currents in human atrial myocytes. Whole-cell patch-clamp of enzymatically isolated atrial myocytes from 11 cardiac surgical patients aged between 29 days and 74 years revealed potent time- and concentration-dependent (IC50 = 4.8 +/- 0.4 mumol/l), but age-, voltage-, and frequency-independent propafenone inhibition of transient outward current. Time course of apparent transient outward current inactivation was best described by a single exponential process in the absence of propafenone and by a double exponential model in its presence, with drug-concentration-dependent acceleration of the fast exponential component. Neither voltage dependence of steady-state transient outward current inactivation nor time course of recovery from inactivation was affected by propafenone. Significant inhibition (P < 0.05) of the ultra-rapidly activating delayed rectifier and inwardly rectifying currents was observed only in the presence of > or = 10 mumol/l propafenone. These actions of propafenone could explain its repolarization prolonging effect and might contribute to clinical electrophysiologic responses which have been documented in patients of all ages.
本研究旨在确定普罗帕酮对人心房肌细胞复极化电流的细胞电药理学效应。对11例年龄在29天至74岁之间的心脏手术患者经酶分离的心房肌细胞进行全细胞膜片钳研究，结果显示普罗帕酮对瞬时外向电流具有强大的时间和浓度依赖性（IC50 = 4.8 +/- 0.4 μmol/L）抑制作用，但与年龄、电压和频率无关。在不存在普罗帕酮时，表观瞬时外向电流失活的时间进程最好用单指数过程描述，而在其存在时则用双指数模型描述，快速指数成分的加速与药物浓度有关。普罗帕酮既不影响稳态瞬时外向电流失活的电压依赖性，也不影响失活后的恢复时间进程。仅在存在≥10 μmol/L普罗帕酮时，才观察到超快速激活延迟整流电流和内向整流电流受到显著抑制（P < 0.05）。普罗帕酮的这些作用可以解释其复极化延长效应，并可能有助于解释在各年龄段患者中记录到的临床电生理反应。
