Effect of amiodarone on Kv1.4 channel C-type inactivation: Comparison of its effects with those induced by propafenone and verapamil

As the major component of I_{to (slow)}, Kv1.4 channel plays an important role in repolarization of cardiac myocytes. C-type inactivation is one of Kv1.4 inactivation and can be affected by open channel blockers. We used the two-electrode voltage clamp technique to observe the effect of amiodarone on Kv1.4 C-type inactivation and compare amiodarone's effects on Kv1.4 with propafenone and verapamil. Our data show that those three antiarrhythmic drugs blocked fKv1.4ΔN (N-terminal deleted Kv1.4 channel from ferret heart) in voltage- and frequent-dependent manners. The amiodarone's IC₅₀ was 489.23 ±4.72 μM, higher than that of propafenone (98.97 ± 1.13 μM) and verapamil (263.26 ± 6.89 μM) for fKv1.4ΔN channel (+50 mV). After application of amiodarone, propafenone and verapamil, fKv1.4ΔN inactivation becomes bi-exponential: the faster portion of inactivation (drug-induced inactivation) and the slower portion of inactivation (C-type inactivation). Amiodarone and verapamil fastened C-type inactivation in fKv1.4ΔN, but propafenone did not. Unlike propafenone that had no effect on fKv1.4ΔN recovery, amiodarone and verapamil slowed recovery in fKv1.4ΔN.