--- - |2 Summary 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 ± 0.87 μmol/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 2 Hz 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. - 'Clinical and Experimental Pharmacology and Physiology, Volume 45, Issue 12, Page 1286-1292, December 2018. '