Noritsugu Tohse (#) and Morio Kanno
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo 060, Japan
(#) Present address: Department of Physiology, School of Medicine, Sapporo Medical University, Sapporo 060, Japan
Abstract: The effects of dofetilide (UK 68798) on membrane currents were examined in isolated sinoatrial node cells of rabbits by using patch clamping. At a concentration of 1 microM, dofetilide decreased the delayed rectifier K+ current (Ik) (50.2+-10.2%, mean+-S.E.). The Ca2+ current was slightly decreased during the application of dofetilide. However, the decrease in thc current may be attributed to the ''run down'' phenomenon. The drug did not affect the hyperpolarization-activated inward current. Therefore, dofetilide exhibited class III antiarrhythmic activity in rabbit sinoatrial node cells. Similarly, E-4031 (1-[2-(6-methyl-2-pyridyl)ethyl]- 4-(4-methylsulfonylaminobenzoyl)pireridine) (1 microM), a standard class III agent, also showed specific inhibition of Ik . Furthermore, dofetilide depolarized the maximum diastolic potentials, reduced the slope of the pacemaker potential and then abolished spontaneously firing action potentials in the nodal cells. The results demonstrate that dofetilide may produce negative chronotropic effects as a result of its class III activity.
Keywords: Dofetilide, E-4031, Ion channel, Delayed rectifier K+ current, Sinoatrial node cell
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