Follmer C H, Aomine M, Yeh J Z, Singer D H
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois.
J Pharmacol Exp Ther. 1987 Oct;243(1):187-94.
Sodium current (INa) block by amiodarone (AMI) was investigated in isolated single Purkinje and ventricular myocardial cells using the single suction-pipette voltage-clamp technique. AMI produced marked resting block that was enhanced at low holding potentials, findings consistent with a shift in the steady-state INa availability curve to more negative potentials (-16 +/- 3 mV). Resting block was not associated with any change in the time course of INa decay during a depolarizing clamp step. AMI also produced use-dependent block in conjunction with increases in rate (0.5-5.0 Hz) and pulse duration (2-200 msec). These changes are consistent with a slowing of the recovery from inactivation of the sodium channel. Brief depolarizing pulses produced little use-dependent block, suggesting that the onset of drug-induced block is slow. Thus, AMI blocks INa and shifts the availability curve in isolated myocytes, both of which contribute to the net tonic block. The results suggest that both rested state and inactivated state sodium channel block are factors in AMI's antiarrhythmic efficacy.
采用单吸管电压钳技术，在分离的单个浦肯野细胞和心室肌细胞中研究了胺碘酮（AMI）对钠电流（INa）的阻断作用。AMI产生明显的静息阻断，在低钳制电位时增强，这一结果与稳态INa可用性曲线向更负电位（-16±3 mV）的移位一致。静息阻断与去极化钳制步骤期间INa衰减的时间进程的任何变化均无关。AMI还与频率增加（0.5 - 5.0 Hz）和脉冲持续时间增加（2 - 200毫秒）一起产生使用依赖性阻断。这些变化与钠通道失活恢复减慢一致。短暂的去极化脉冲产生的使用依赖性阻断很少，表明药物诱导的阻断起效缓慢。因此，AMI阻断INa并使分离的心肌细胞中的可用性曲线移位，这两者都导致净强直阻断。结果表明，静息状态和失活状态的钠通道阻断都是AMI抗心律失常疗效的因素。
