Effects of MS-551, a new class III antiarrhythmic drug, on action potential and membrane currents in rabbit ventricular myocytes

Abstract

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.