A new class III antiarrhythmic drug, MS-551, blocks the inward rectifier potassium channel in isolated guinea pig ventricular myocytes
Sato, R.; Koumi, S.; Hisatome, I.; Takai, H.; Aida, Y.; Oyaizu, M.; Karasaki, S.; Mashiba, H.; Katori, R.
Journal of Pharmacology and Experimental Therapeutics 274(1): 469-474
1995
ISSN/ISBN: 0022-3565 PMID: 7616432 Document Number: 451597
We have studied the effects of MS-551 on the inward rectifier potassium channel (I-K1) in isolated guinea-pig ventricular myocytes by use of whole-cell and single-channel recording techniques. MS-551 (5 mu-M) blocked the I-K1 current. The percent blockade of the peak and steady-state I-K1 current by MS-551 was constant at each test potential. In contrast 50 mu-M MS-551 failed to block either the sodium or the calcium current. Under cell-attached patch conditions, MS-551 reduced the open probability of I-K1 channel activity by prolonging the interburst interval without changing either the unitary amplitude or the equilibrium potential. The blockade of I-K1 was concentration-dependent. MS-551 did not change either the mean open time or mean closed time within a burst. Extracellular acidification (pH 6.4) strongly attenuated the effect of MS-551 on the open probability of I-K1 channel activity when compared with its effect at pH 7.4. In summary, our results demonstrated that MS-551 blocked the I-K1 channel. The neutral form of this drug molecules may penetrate the cardiac cell membrane via a hydrophobic pathway to block the steady-state I-K1 current by reduction of open probability.