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电压钳制兔窦房结标本中昔苯唑啉的电生理研究。

Electrophysiological study of cibenzoline in voltage-clamped rabbit sinoatrial node preparations.

作者信息

Kotake H, Matsuoka S, Ogino K, Takami T, Hasegawa J, Mashiba H

出版信息

J Pharmacol Exp Ther. 1987 Jun;241(3):982-6.

PMID:3598914
Abstract

Effects of cibenzoline (0.1-30 microM) on membrane potentials and currents were investigated in rabbit sinoatrial node cells using conventional microelectrode and double microelectrode voltage clamp methods. Cibenzoline reduced the heart rate, the maximum rate of rise and the action potential amplitude in a dose-dependent manner. At the same time, the action potential duration at half-amplitude was prolonged, and the slope of phase 4 depolarization was decelerated. The voltage clamp experiment revealed that cibenzoline (7-30 microM) depressed the slow inward current, the time-dependent potassium outward current and the hyperpolarization activated current. Neither the kinetic variable of the time-dependent potassium outward current nor the decay time of the outward current tail was altered by the drug perfusion. The results suggest that cibenzoline exerts a depressant effect on the electrical activity of sinoatrial node cells and that the depression of the currents induced by cibenzoline is due to a reduction in conductances of the current systems.

摘要

采用传统微电极和双微电极电压钳方法,研究了西苯唑啉(0.1 - 30微摩尔)对兔窦房结细胞膜电位和电流的影响。西苯唑啉以剂量依赖性方式降低心率、最大上升速率和动作电位幅度。同时,动作电位半幅持续时间延长,4期去极化斜率减慢。电压钳实验表明,西苯唑啉(7 - 30微摩尔)抑制慢内向电流、时间依赖性钾外向电流和超极化激活电流。药物灌注未改变时间依赖性钾外向电流的动力学变量或外向电流尾电流的衰减时间。结果表明,西苯唑啉对窦房结细胞的电活动具有抑制作用,且西苯唑啉诱导的电流抑制是由于电流系统电导降低所致。

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引用本文的文献

1
Cibenzoline inhibits diazoxide- and 2,4-dinitrophenol-activated ATP-sensitive K+ channels in guinea-pig ventricular cells.西苯唑啉抑制豚鼠心室细胞中由二氮嗪和2,4-二硝基苯酚激活的ATP敏感性钾通道。
Br J Pharmacol. 1993 Feb;108(2):549-56. doi: 10.1111/j.1476-5381.1993.tb12839.x.
2
Effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig ventricular cells.新型 I a 类抗心律失常药物西苯唑啉对豚鼠心室肌细胞膜离子电流和动作电位的影响。
Naunyn Schmiedebergs Arch Pharmacol. 1994 Aug;350(2):167-73. doi: 10.1007/BF00241092.
3
Chronotropic effect of nizofenone fumarate in rabbit sino-atrial node in vitro.
富马酸尼唑苯酮对家兔离体窦房结的变时性作用。
Br J Pharmacol. 1988 Dec;95(4):1175-80. doi: 10.1111/j.1476-5381.1988.tb11753.x.
4
Cibenzoline. A review of its pharmacological properties and therapeutic potential in arrhythmias.西苯唑啉。其药理学特性及在心律失常治疗中的潜在应用综述。
Drugs. 1992 May;43(5):734-59. doi: 10.2165/00003495-199243050-00008.