Účinky sigma ligandu haloperidolu na membránové proudy kardiomyocytů potkana

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Title in English Effects of Sigma Receptor Ligand Haloperidol on Cardiac Excitability
Authors

NOVÁKOVÁ Marie BÉBAROVÁ Markéta PÁSEK Michal MATEJOVIČ Peter TARABOVÁ Bohuslava LACINOVÁ Ĺubica

Year of publication 2005
Type Article in Proceedings
Conference Zborník prác a abstraktov prezentovaných na 81. Fyziologických dňoch
MU Faculty or unit

Faculty of Medicine

Citation
Field Physiology
Keywords haloperidol; cardiac ionic currents; sigma receptor
Description Sigma receptor ligand haloperidol is a psychotropic drug used in the treatment of various psychiatric disorders. Severe cardiovascular side effects (mostly ventricular arrhythmias) have been reported. Thus, we have investigated the effects of haloperidol on the sodium current INa and potassium currents, the transient outward current Ito, the current at the end of 250ms-impulse IK,end (that is mainly composed of the delayed rectifier current IK) and the inward rectifier current IK1. Experiments were performed on enzymatically isolated rat ventricular cardiomyocytes by whole cell patch clamp technique at room temperature. Haloperidol causes reversible and concentration-dependent inhibition of sodium and potassium membrane currents in rat ventricular cardiomyocytes with the highest effectivity on INa and Ito. In the case of potassium currents, the inhibition was voltage-independent. The observed acceleration of apparent inactivation of Ito after aplication of haloperidol is a typical sign of interaction with Ito-channels in the open state. Simultaneously, the negligible effect of haloperidol on the steady state inactivation curve of Ito implies no interaction with the channels in the inactivated state. However, further examination with lower haloperidol concentrations is needed in order to explain frequent ventricular dysrythmias in haloperidol-treated patients.
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