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

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Abstract
Electrophysiological effects of MS‐551, a new class III antiarrhythmic drug, were examined and compared with those of (+)‐sotalol in rabbit ventricular cells. In rabbit ventricular muscles stimulated at 1.0 Hz, MS‐551 (0.1–10 μm) and (+)‐sotalol (3–100 μm) prolonged action potential duration (APD) and effective refractory period without affecting the maximum upstroke velocity of phase 0 depolarization . The class III effect of MS‐551 was approximately 30 times more potent than that of (+)‐sotalol. Class III effects of MS‐551 and (+)‐sotalol showed reverse use‐dependence, i.e., a greater prolongation of APD at a longer cycle length. In rabbit isolated ventricular cells, 3 μm MS‐551 and 100 μm sotalol inhibited the delayed rectifier potassium current (IK) which was activated at more positive potentials than −50 mV and saturated around + 20 mV. MS‐551 at a higher concentration of 10 μm decreased the transient outward current (Ito) and the inward rectifier potassium current (IK1) although 100 μm sotalol failed to inhibit these currents. MS‐551 is a non‐specific class III drug which can inhibit three voltage‐gated K+ channels in rabbit ventricular cells.

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