<SHORT REPORTS>Comparative Investigation of New Class-III Antiarrhythmic Drugs, E-4031 and MS-551, on Action Potentials and Ionic Currents in single Rabbit Ventricular Myocytes

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Effects of new class-III antiarrhythmic agents, E-4031 and MS-551, were investigated on action potential duration (APD) and ionic currents in single rabbit ventricular myocytes. Under 1.0 Hz steady-state stimulation, both E-4031 (1μM) and MS-551(10 μM) prolonged APD. The prolongation of APD by E-4031 (1μM) was attenuated at higher stimulation frequencies, showing a reversed frequency dependence. Conversely, the prolongation of APD by MS-551 (10μM) was enhanced at higher rates. In myocytes treated with E-4031 1μM, the prolongation ofAPD of a test action potential which was preceded by a train of 1.0 Hz stimulation was maintaintained at rest durations ranging from 1.0 to 30 sec. The APD prolongation by MS-551 (10μM) however, decreased progressively as the rest duration increased. In voltage clamp experiments, both E-4031 (1μM) and MS-551 (10μM) inducedsignificant decreses in outward rectifier potassium current (1_k) significantly, but induced no effects on transient outward current (1_<to>). These findings suggest that E-4031 and MS-551 produce differing frequency dependencies in clas-III action and that further ionic mechanisms should be clarified.
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