Electrophysiological effects of ibutilide on the delayed rectifier K+ current in rabbit sinoatrial and atrioventricular node cells

Biophysical and pharmacological characteristics of the delayed rectifier K current (I-K) of rabbit sinoatrial (SA) node and atrioventricular (AV) nod e cells have been studied using the whole-cell patch clamp technique togeth er with a recently developed antiarrhythmic agent, ibutilide. Ibutilide is a potent blocker of the rapid delayed rectifier K+ current, I-Kr. Superfusi on with ibutilide (10(-7) M) caused a decrease in the spontaneous firing fr equency, depolarization of the maximal diastolic potential and prolongation of the action potential duration in both SA and AV node cells. In whole ce ll voltage clamp experiments done on myocytes from SA node, ibutilide (10(- 7) M) blocked I-K strongly (40%) and had smaller effects on Ca2+ current (1 0%) and hyperpolarization-activated inward current, I-f (11%). In AV node c ells, the corresponding reductions were I-K (68%), I-Ca (13%) and I-f (10%) , respectively. A 10-fold increase in the concentration of ibutilide furthe r decreased I-K in SA node cells (67 +/- 8%), and blocked I-K almost comple tely in AV node cells. These results are consistent with the hypothesis tha t the delayed rectifier K+ current in SA node cell is generated by both I-K r and I-Ks, whereas I-Kr predominates in AV node cells. Knowledge of the di fferences in the distribution of I-Kr,as well as the different sensitivity to blockers of I-Kr in nodal cells, is important for understanding modifica tions of the automaticity, conduction velocity, and refractoriness by class III antiarrhythmic agents. (C) 2000 Elsevier Science B.V. All rights reser ved.