کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2536649 | 1559165 | 2006 | 9 صفحه PDF | دانلود رایگان |
Although sigma ligand haloperidol is known to affect repolarization in heart, its effect on potassium currents in cardiomyocytes has not yet been studied. We analyzed the effect of 1 μmol/l haloperidol on transient outward K+ current (Ito) in enzymatically isolated rat right ventricular cardiomyocytes using the whole-cell patch-clamp technique at room temperature. Haloperidol induced a decrease of amplitude and an acceleration of apparent inactivation of Ito, both in a voltage-independent manner. The averaged inhibition of Ito, evaluated as a change of its time integral, was 23.0 ± 3.2% at stimulation frequency of 0.1 Hz. As a consequence of slow recovery of Ito from the haloperidol-induced block (time constant 1482 ±783 ms), a cumulation of the block up to about 40% appeared at 3.3 Hz. We conclude that haloperidol causes a voltage-independent block of Ito that cumulates at higher stimulation frequencies. Based on the computer reconstruction of experimental data, a block of Ito-channels in both open and open-inactivated states appears to be likely mechanism of haloperidol-induced inhibition of Ito.
Journal: European Journal of Pharmacology - Volume 550, Issues 1–3, 21 November 2006, Pages 15–23