Abstract

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.