NIBENTAN INHIBITS THE DELAYED RECTIFIER P OTASSIUM CURRENT IN RAT VENTRICULAR MYOCYTES

A whole-cell voltage-clamp analysis of the effect of nibentan, a novel class III antiarrhythmic agent, ore the K+ currents was made in rat v entricular myocytes. In these cells, nibentan (2,5 to 25 mu mol/l) dec reased within 10 min the delayed rectifier outward K+ current, I-k, in a concentration dependent manner (IC50 15 mu mol/l). In contrast, the drug was without significant effects on the transient outward and on inward rectifier K+ current. The inhibitory effect of nibentan on I-k was rate-dependent and decreased with increase in stimulation frequenc y (0,1 - 1,0 Hz). As experiments showed, the rate dependence of nibent an affect on I-k could not be a result of a voltage dependence of bind ing of the drug to K+ channel. Thee effects were observed at clinicall y relevant concentrations and may explain lengthening of cardiac repol arization induced by nibentan and contribute to its antiarrhythmic act ion.