title: Effect of haloperidol on transient outward potassium current in rat ventricular myocytes.
abstract: 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).
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Komenského nám. 2, 662 43 Brno, Czech Republic. bebarova.ifmu@centrum.cz
authors.forename: Markéta
authors.initials: M
authors.lastname: Bébarová
authors.forename: Peter
authors.initials: P
authors.lastname: Matejovic
authors.forename: Michal
authors.initials: M
authors.lastname: Pásek
authors.forename: Marie
authors.initials: M
authors.lastname: Nováková
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D015221:Potassium Channels; D017480:Receptors, sigma; D006220:Haloperidol