Effect of haloperidol on transient outward potassium current in rat ventricular myocytes.
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 micromol/l haloperidol on transient outward K(+) current (I(to)) 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 I(to), both in a voltage-independent manner. The averaged inhibition of I(to), 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 I(to) 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 I(to) that cumulates at higher stimulation frequencies. Based on the computer reconstruction of experimental data, a block of I(to)-channels in both open and open-inactivated states appears to be likely mechanism of haloperidol-induced inhibition of I(to).
Bébarová
Markéta
M
Department of Physiology, Faculty of Medicine, Masaryk University, Komenského nám. 2, 662 43 Brno, Czech Republic. bebarova.ifmu@centrum.cz
Matejovic
Peter
P
Pásek
Michal
M
Nováková
Marie
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004594:Electrophysiology; D006220:Haloperidol / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015233:Models, Statistical; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects
D014150:Antipsychotic Agents; D015221:Potassium Channels; D017480:Receptors, sigma; D006220:Haloperidol