Chronotropic effect of nizofenone fumarate in rabbit sino-atrial node in vitro

1. The effects of nizofenone fumarate were studied on the membrane potentials and currents of rabbit sino-atrial node preparations by means of the double-microelectrode voltage clamp method. 2. In spontaneously firing pacemaker cells, nizofenone (above 1 microM) decreased the heart rate. Above 3 microM, nizofenone reduced the maximum upstroke velocity, the amplitude of the action potential and the slope of the phase 4 depolarization, and prolonged the action potential duration at 50% repolarization. 3. Under voltage clamp conditions, nizofenone decreased the slow inward current and the time-dependent potassium outward current in a dose-dependent manner. 4. These findings suggest that nizofenone exerts an inhibitory action on the automaticity of sinoatrial node preparations via effects on both inward and outward currents.