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.
Kotake
H
H
1st Department of Internal Medicine, Tottori University, Yonago, Japan.
Nawada
T
T
Matsumoto
T
T
Kitamura
H
H
Kaneda
T
T
Hasegawa
J
J
Mashiba
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology
D007093:Imidazoles; C016910:nizofenone; D011188:Potassium