Membrane activity of class III antiarrhythmic compounds; a comparison between ibutilide, d-sotalol, E-4031,...

This study compares the membrane activity of ibutilide, d-sotalol, sematilide, E-4031 and dofetilide on single ventricular cells under identical experimental conditions. We found that ibutilide and dofetilide produced a 'bell-shaped' concentration-dependent effect on action potential duration. Ionic current measurement showed that ibutilide, at 10(-8) M, increased a late inward current; the other compounds had either no effect or decreased it. Moreover, only ibutilide, at a high concentration of 10(-5) M, increased an outward current, as oppose to a uniform depression of IK by d-sotalol, sematilide, E-4031 and dofetilide, and the depression of IK by the latter compounds could be reversed by 10(-5) M ibutilide. Finally, low concentration of ibutilide could further prolong the action potential duration that had already been prolonged by a K+ channel blocker, but a high concentration of ibutilide did just the opposite by reversing the prolongation caused by K+ channel blockers. Therefore, action potentials agree well with the ionic current results. Possible mechanistic advantage of ibutilide over K+ channel blockers was discussed.