Yatani A, Brown A M, Schwartz A
J Pharmacol Exp Ther. 1986 Apr;237(1):9-17.
The effects of bepridil, a new Ca channel blocking agent with reported antiarrhythmic action, were examined in single isolated ventricular cells using whole-cell patch clamp techniques. Ca currents were studied in guinea-pig ventricular cells and Na currents were studied in cultured ventricular cells from neonatal rat, a preparation which is more suitable for Na current measurements than guinea pig. At low frequencies (0.1 Hz) and negative holding potentials (-50 mV for Ca currents and -100 mV for Na currents), bepridil produced a concentration-dependent decrease in both Ca and Na currents without any significant change in the current-voltage relations. Concentration-response curves for block of Ca and Na channels were fitted by a one-to-one drug-receptor occupancy model. Half-blocking concentrations (IC50) of bepridil were 5 x 10(-7) M for Ca currents and 3 X 10(-5) M for Na currents. Bepridil had no effect on the inwardly rectifying K current and the time-dependent outward current. The effects of bepridil on Ca and Na currents depend upon the holding potential. Inactivation curves of the Ca and Na currents were shifted to more negative potentials by the drug. The recovery of both the Ca and Na currents from inactivation was always prolonged by bepridil and the repriming of both currents usually displayed an added exponential component, attributed to slow release of the drug from the channels. The results indicate that bepridil, by inhibiting both Ca and Na currents, may have clinical usefulness in the treatment of certain ischemia-induced ventricular arrhythmias.
使用全细胞膜片钳技术，在单个分离的心室细胞中研究了新型钙通道阻滞剂苄普地尔（据报道具有抗心律失常作用）的效应。在豚鼠心室细胞中研究钙电流，在新生大鼠培养的心室细胞中研究钠电流，该制备物比豚鼠更适合用于钠电流测量。在低频（0.1Hz）和负的钳制电位（钙电流为-50mV，钠电流为-100mV）下，苄普地尔使钙电流和钠电流均呈浓度依赖性降低，而电流-电压关系无任何显著变化。钙通道和钠通道阻滞的浓度-反应曲线用一对一的药物-受体占据模型拟合。苄普地尔对钙电流的半数阻滞浓度（IC50）为5×10^(-7)M，对钠电流为3×10^(-5)M。苄普地尔对内向整流钾电流和时间依赖性外向电流无影响。苄普地尔对钙电流和钠电流的效应取决于钳制电位。药物使钙电流和钠电流的失活曲线向更负的电位移动。苄普地尔总是延长钙电流和钠电流从失活状态的恢复，并且两种电流的再激活通常显示出一个额外的指数成分，这归因于药物从通道的缓慢释放。结果表明，苄普地尔通过抑制钙电流和钠电流，可能在治疗某些缺血性诱发的室性心律失常方面具有临床应用价值。
