Prevailing Effects of Ibutilide on Fast Delayed Rectifier K+ Channel.

ABSTRACT

Effects of ibutilide, a class III antiarrhythmic drug, on delayed rectifier potassium currents (IK) in freshly isolated guinea pig ventricular myocytes were studied. Experiments were performed using the whole-cell configuration of patch-clamp technique under blockade of L-type calcium currents (Cav1). Ibutilide at concentrations ranging between 10 nM and 100 µM inhibited IKr in dose-dependent manner with a half maximal effective concentration of 2.03 ± 0.74 µM (n = 5-10). The amplitude of tail currents activated by prepulse to + 20 mV was decreased from 253 ± 52 to 130 ± 25 pA (n = 8, p < 0.01) in the presence of 1 µM ibutilide. The envelope test revealed time-dependent changes in ratio of IK-tail/ΔIK during 0.2-2 s pulse durations in the absence of drug. With ibutilide, regardless of pulse duration, a relatively constant ratio was estimated, indicative of predominant involvement of IKr component. The slow IKs persisted to greater extent even at 100 µM ibutilide revealing a distinguishable selectivity toward the IKr component.