EFFECTS OF DOFETILIDE ON MEMBRANE CURRENTS IN SINOATRIAL NODE CELLS OF RABBIT

The effects of dofetilide (UK 68798) on membrane currents were examine d in isolated sinoatrial node cells of rabbits by using patch clamping . At a concentration of 1 mu M, dofetilide decreased the delayed recti fier K+ current (I-K) (50.2+/-10.2%, mean+/-S.E.). The Ca2+ current wa s slightly decreased during the application of dofetilide. However, th e decrease in the current may be attributed to the ''run down'' phenom enon. The drug did not affect the hyperpolarization-activated inward c urrent. Therefore, dofetilide exhibited class III antiarrhythmic activ ity in rabbit sinoatrial node cells. Similarly, E-4031 ethyl]-4-(4-met hylsulfonylaminobenzoyl)Pireridine) (1 mu M), a standard class III age nt, also showed specific inhibition of I-K. Furthermore, dofetilide th e polarized the maximum diastolic potentials, reduced the slope of the pacemaker potential and then abolished spontaneously firing action po tentials in the nodal cells. The results demonstrate that dofetilide m ay produce negative chronotropic effects as a result of its class III activity.