H. Nakaya et al., EFFECTS OF MS-551, A NEW CLASS-III ANTIARRHYTHMIC DRUG, ON ACTION-POTENTIAL AND MEMBRANE CURRENTS IN RABBIT VENTRICULAR MYOCYTES, British Journal of Pharmacology, 109(1), 1993, pp. 157-163
1 Electrophysiological effects of MS-551, a new class III antiarrhythm
ic drug, were examined and compared with those of (+)-sotalol in rabbi
t ventricular cells. 2 In rabbit ventricular muscles stimulated at 1.0
Hz, MS-551 (0.1-10 mum) and (+)-sotalol (3 100 mum) prolonged action
potential duration (APD) and effective refractory period without affec
ting the maximum upstroke velocity of phase 0 depolarization (V(max)).
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 (+)-sotal
ol showed reverse use-dependence, i.e., a greater prolongation of APD
at a longer cycle length. 4 In rabbit isolated ventricular cells, 3 mu
m MS-551 and 100 mum sotalol inhibited the delayed rectifier potassium
current (I(K)) which was activated at more positive potentials than -
50mV and saturated around + 20 mV. 5 MS-551 at a higher concentration
of 10 mum decreased the transient outward current (I(to)) and the inw
ard rectifier potassium current (I(K1)) although 100 mum sotalol faile
d to inhibit these currents. 6 MS-551 is a non-specific class III drug
which can inhibit three voltage-gated K+ channels in rabbit ventricul
ar cells.