Interaction of haloperidol with L-type voltage dependent calcium channels
| Authors | |
|---|---|
| Year of publication | 2005 |
| Type | Article in Periodical |
| Magazine / Source | Physiological Research |
| MU Faculty or unit | |
| Citation | |
| Field | Physiology |
| Keywords | sigma receptor; haloperidol; L-type calcium channel |
| Description | Haloperidol is neuroleptic agent, effective in the treatment of various psychiatric disorders, such as schizophrenia or mania. Cardiac arrhythmias and other severe cardiovascular side effects have been associated with this therapy. We have investigated effects of haloperidol on currents through cardiac calcium channels in native tissue, i.e., in cardiomyocytes, and in expression system, i.e., in HEK 293 cells. Cardiomyocytes were enzymaticaly isolated from adult rat ventricles. HEK 293 cells were transiently transfected with cDNAs encoding a and b isoforms of the a1 subunit of CaV1.2 calcium channel together with b2a and a2d subunits. a1C-a isoform is expressed mostly in cardiac tissue, while a1C-b is prevalent in smooth muscles. Currents were measured using whole cell configuration of patch-clamp method. In HEK 293 cells transfected with a1C-b subunit 10 ľmol/l haloperidol inhibited approximately 58% of inward current amplitude measured in peak of IV relation. The inhibition was reversible and voltage dependent. Approximately 55% of current through cardiac a1C-a subunit isoform expressed in HEK 293 cells was blocked by the same concentration of haloperidol. Shift of the reversal potential was observed in both splice variants of CaV1.2 calcium channel in the presence of haloperidol. This change may be induced by alteration of ion selectivity of the expressed channel. 10 ľmol/l of haloperidol inhibited also current through the L-type calcium channels in rat cardiomyocytes. This block was rapid and reversible. In conclusion, inhibition of inward currents through CaV1.2 calcium channels in model HEK 293 cells and in native cardiomyocytes by 10 ľmol/l haloperidol was observed. Used concentration was one order higher than therapeutic plasma concentration, therefore its expected effects in patients will be more subtle. Nevertheless, inhibition of cardiac calcium current still may contribute to observed side effects of haloperidol. |
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