Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation.

Flecainide, a class Ic antiarrhythmic drug, has been anecdotally reported to improve myotonia, but little is known about its kinetics on human skeletal muscle sodium channels applicable in vivo. Here we explored the anti-myotonic action of flecainide for human skeletal muscle sodium channels heterologously expressed in cultured cells. Flecainide blocked sodium channels in a highly state-dependent manner with 20-fold difference in IC(50) between use-dependent and tonic blocks. When pulses of brief depolarization simulating myotonia were applied from a holding potential of -90 mV, flecainide at therapeutic concentrations significantly blocked sodium currents. Flecainide slowed the time course of recovery but most channels recovered from block within 10-20 s. In contrast to mexiletine, flecainide did not markedly block sodium current during prolonged depolarization, suggesting an open-channel blocking action. Considering the slow recovery from block and the specific action against repetitive depolarization, flecainide may represent a potent therapeutic agent for myotonia.