Effect of propafenone on Kv1.4 inactivation

Interactions between antiarrhythmic drugs and ion channels are important subjects in the field of cardiovascular electro-pharmacology. This study explores the relationship between propafenone and C-type inactivation of Kv1.4 channel. fKv1.4ΔN, a ferret Kv1.4 N-terminal deleted mutant, was employed in this study. fKv1.4ΔN cRNA was injected into Xenopus oocytes to express fKv1.4ΔN channel and two electrode voltage clamp technique was used to record the current. We found that fKv1.4ΔN channel current was rapidly depressed in a frequency-dependent manner and meanwhile, C-type inactivation in this channel was increased more than 7 folds in the presence of 100 μM propafenone. While propafenone has no effect on Kv1.4ΔN recovery. All the results indicate that propafenone blocks Kv1.4ΔN channel through intracellular bindings and that binding of propafenone with Kv1.4ΔN channel leads to a conformational change on the extracellular site which accelerates C-type inactivation, suggesting that propafenone, as an open channel blocker, may affect the mechanism of C-type inactivation.