This study examined the inhibitory effect of flecainide, a class 1c antiarrhythmic agent (Na+ channel blocker), on voltage-dependent K+ (Kv) channels in smooth muscle cells isolated from coronary arteries. Flecainide decreased the vascular Kv channel current in a dose-dependent manner with an IC50 value of 5.90±0.87μmol/L and a Hill coefficient of 0.77±0.06. Although the steady-state activation curve was not affected by flecainide, it shifted the steady-state inactivation curves toward a more negative potential. Application of train pulses such as 1 or 2Hz did not change the flecainide-induced inhibition of Kv channels, indicating that the inhibitory effect of flecainide was not use-dependent. Using perforated-patch clamp experiments, we found that inhibition of Kv channels by flecainide caused membrane depolarization. Together, these results suggest that flecainide inhibits Kv channels in a concentration-dependent, but not use-dependent manner by changing the inactivation gating properties. Furthermore, Kv channel inhibition by flecainide occurs regardless of Na+ channel inhibition.