Voltage- and use-dependent effects of lidocaine on sodium current in rat single ventricular cells.
Voltage- and use-dependent effects of lidocaine on sodium current in rat single ventricular cells.
复制标题
利多卡因对大鼠单心室细胞钠电流的电压和使用依赖性影响。
DOI：
10.1161/01.res.52.5.557
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发表时间：
1983
影响因子：
20.1
通讯作者：
Josephson,IR
中科院分区：
文献类型：
--
作者：
Sanchez-Chapula,J;Tsuda,Y;Josephson,IR
我们利用单个大鼠心室细胞，比较了局麻药利多卡因和苯佐卡因对钠电流的阻断作用，以进一步了解局麻药与心脏钠通道相互作用的电压依赖性和动力学。我们使用了一种混合电压钳系统，该系统采用了一个吸液管来通过电流和内部灌注，一个微电极来测量膜电位。当不频繁施加测试脉冲时，利多卡因（20微米）和苯佐卡因（100微米）对钠电流产生定性相似的影响。这两种试剂都降低了钠的峰值电流，而不产生电流-电压曲线的移位。然而，他们确实将钠电流的失活曲线转向了超极化电位；利多卡因和苯佐卡因的V0.5分别移动了-9.5 mV和-5 mV。利多卡因产生了显著的使用依赖性效应，与电压步骤的持续时间成正比。苯佐卡因只产生最小的使用依赖性效应。利多卡因阻滞的特性表明，该药物优先结合失活的钠通道，并且与静息通道的解离依赖于电压。利多卡因和苯佐卡因在脂溶性和分子量上的差异可能解释了它们对钠电流的使用依赖性阻断作用的差异。
We compared the blocking effects of the local anesthetics, lidocaine and benzocaine, on the sodium current, using single rat ventricular cells to obtain further information about the voltage dependence and kinetics of local anesthetic interaction with cardiac sodium channels. We used a hybrid voltage clamp system which employed a suction pipette for passing current and internal perfusion, and a microelectrode for membrane potential measurement. Lidocaine (20 microM) and benzocaine (100 microM) produced qualitatively similar effects on sodium current when test pulses were applied infrequently. Both of these agents decreased the peak sodium current without producing a shift of the current-voltage curve. They did, however, shift the inactivation curves of sodium current to hyperpolarized potentials; the V0.5 was shifted by -9.5 mV for lidocaine and by -5 mV for benzocaine. Lidocaine produced a significant use-dependent effect that was proportional to the duration of the voltage step. Benzocaine produced only minimal use-dependent effects. The characteristics of the lidocaine block suggest that this agent binds preferentially to inactivated sodium channels and that dissociation from resting channels is voltage-dependent. The differences in lipid solubility and molecular weight between lidocaine and benzocaine may explain the differences in their use-dependent blocking effects on sodium current.