Atrial fibrillation (AF) is caused by an interaction between an "initiating trigger" such as ectopic activity in the pulmonary vein (PV) and a "vulnerable status" such as an atrial effective refractory period (ERP) shortening. Controlling both causal factors is an ideal therapeutic strategy for AF, but it is difficult to be achieved by existing drugs. We hypothesized that the blockade of persistent component of the sodium current (late I_Na; I_NaL) could be an innovative approach for AF treatment. Using NCC-3902; a selective I_NaL blocker, we examined whether inhibition of I_NaL has an effect on ectopic activity, atrial ERP, and AF induction.

NCC-3902 blocked I_NaL, but had no effect on other major cardiac ion channel currents stably expressed in cell lines. In isolated guinea pig PV, NCC-3902 decreased the automatic firing frequency of the myocardium. In canine rapid atrial pacing models, NCC-3902 prolonged the ERP and intra atrial conduction time in a dose-dependent manner. In addition, NCC-3902 suppressed AF induction without proarrhythmic potentials. Our results suggest that the blockade of I_NaL could achieve an ideal AF management with controlling both an "initiating trigger" and a "vulnerable status" without proarrhythmic potentials. A novel I_NaL blocker, NCC-3902, could bring more effective and safer approach for AF treatment.