Publication details

Effects of sigma receptor ligand haloperidol on ionic currents in rat cardiomyocyte

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Year of publication 2006
Type Article in Periodical
Magazine / Source Journal of Molecular and Cellular Cardiology
MU Faculty or unit

Faculty of Medicine

Field Physiology
Keywords sigma receptor;haloperidol;ionic currents;cardiomyocyte
Description Sigma receptor ligand haloperidol is a neuroleptic drug with adverse cardiovascular effects, mainly ventricular arrhythmias. Its effects on the time course of action potential and on the basic ionic currents (sodium current INa, calcium current ICa, and potassium currents Ito,, IK1 and IK,end - current at the end of 250 ms pulse) were studied on enzymatically isolated rat ventricular cardiomyocytes using the whole cell patch clamp technique at room temperature. Haloperidol induced reversible and concentration-dependent inhibition of all investigated membrane currents. 1 ľmol/l inhibited INa by 39 %, ICa by 19.5 %, Ito by 23 % and IK,end by 14%, 10 ľmol/l haloperidol - by 95 %, 22 % 80 % 37 %, respectively, and IK1 by 29 %. Reversible loss of action potential in haloperidol was observed. Inhibition of Ito-amplitude by the drug was accompanied by acceleration of apparent inactivation. Both were voltage-independent. The time course of Ito recovery from inactivation was decelerated in the drug and 9 % of Ito-channels recovered with slow time constant about 1.4 s. It corresponded with a cummulation of inhibition at higher stimulation frequencies (3.3 Hz). We conclude that haloperidol inhibited all the main ionic current in rat cardiomyocytes with profound inhibition of INa that corresponded with loss of action potential. Inhibition of Ito is very likely caused by interaction of haloperidol with Ito-channels in open and in inactivated states as supported by the results of mathematical simulations.
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