| Autor: |
R, Sato, S, Koumi, I, Hisatome, H, Takai, Y, Aida, M, Oyaizu, S, Karasaki, H, Mashiba, R, Katori |
| Rok vydání: |
1995 |
| Předmět: |
|
| Zdroj: |
The Journal of pharmacology and experimental therapeutics. 274(1) |
| ISSN: |
0022-3565 |
| Popis: |
We have studied the effects of MS-551 on the inward rectifier potassium channel (IK1) in isolated guinea-pig ventricular myocytes by use of whole-cell and single-channel recording techniques. MS-551 (5 microM) blocked the IK1 current. The percent blockade of the peak and steady-state IK1 current by MS-551 was constant at each test potential. In contrast 50 microM MS-551 failed to block either the sodium or the calcium current. Under cell-attached patch conditions, MS-551 reduced the open probability of IK1 channel activity by prolonging the interburst interval without changing either the unitary amplitude or the equilibrium potential. The blockade of IK1 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 IK1 channel activity when compared with its effect at pH 7.4. In summary, our results demonstrated that MS-551 blocked the IK1 channel. The neutral form of this drug molecules may penetrate the cardiac cell membrane via a hydrophobic pathway to block the steady-state IK1 current by reduction of open probability. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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