Risperidone reduces K+ currents in human atrial myocytes and prolongs repolarization in human myocardium.
The antipsychotic agent risperidone has been shown to cause QT prolongation. In rabbit heart preparations, we have demonstrated that risperidone markedly lengthened action potential duration and blocked the delayed rectifier current, I(Kr.) The current study was designed to investigate the risperidone effects: (i) on the main K(+) repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings; (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes. We found that: (1) risperidone (3-30 microM) reduced significantly the sustained current, I(sus), and 30 microM decreased significantly the transient outward current I(to) but was without effect on the inward rectifier current I(K1); (2) risperidone (0.3-10 microM) lengthened significantly the final repolarization of the atrial action potential and risperidone (10 microM) markedly lengthened the final repolarization in ventricular myocardium. This study showed that risperidone exerts direct electrophysiological effects on human preparations but only at relatively high concentration.
Gluais
Pascale
P
Laboratoire de Pharmacologie, Faculté de Médecine Henri Warembourg, Pole Recherche, 1 place de Verdun, 59045 Lille Cedex, France. pascale_gluais@yahoo.fr
Bastide
Michèle
M
Grandmougin
Daniel
D
Fayad
Georges
G
Adamantidis
Monique
M
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D018967:Risperidone / Q000494:pharmacology*
D015221:Potassium Channels; D018967:Risperidone