Effects of MS-551, a new class III antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes.
1. Electrophysiological effects of MS-551, a new class III antiarrhythmic drug, were examined and compared with those of (+)-sotalol in rabbit ventricular cells. 2. In rabbit ventricular muscles stimulated at 1.0 Hz, MS-551 (0.1-10 microM) and (+)-sotalol (3-100 microM) prolonged action potential duration (APD) and effective refractory period without affecting the maximum upstroke velocity of phase 0 depolarization (Vmax). The class III effect of MS-551 was approximately 30 times more potent than that of (+)-sotalol. 3. Class III effects of MS-551 and (+)-sotalol showed reverse use-dependence, i.e., a greater prolongation of APD at a longer cycle length. 4. In rabbit isolated ventricular cells, 3 microM MS-551 and 100 microM sotalol inhibited the delayed rectifier potassium current (IK) which was activated at more positive potentials than -50 mV and saturated around +20 mV. 5. MS-551 at a higher concentration of 10 microM decreased the transient outward current (Ito) and the inward rectifier potassium current (IK1) although 100 microM sotalol failed to inhibit these currents. 6. MS-551 is a non-specific class III drug which can inhibit three voltage-gated K+ channels in rabbit ventricular cells.
Nakaya
H
H
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Tohse
N
N
Takeda
Y
Y
Kanno
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011744:Pyrimidinones / Q000494:pharmacology*; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013015:Sotalol / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D015221:Potassium Channels; D011744:Pyrimidinones; C076259:nifekalant; D013015:Sotalol