Haloperidol moderately inhibits cardiovascular L-type calcium current.
Effects of haloperidol on L-type CaV1.2 channel were studied. Calcium current was measured in whole cell patch-clamp using calcium as a charge carrier. Inhibition by haloperidol was investigated in CaV1.2 channel natively expressed in rat cardiac myocytes and recombinant cardiac (CaV1.2a) and vascular (CaV1.2b) splice variants of the channel expressed in HEK 293 cells. Haloperidol inhibited L-type calcium current in a concentration-dependent manner with a threshold of 1 nmol/l. 1 micromol/l haloperidol inhibited 20.6 +/- 3.6% of calcium current amplitude in cardiomyocytes, 25.4 +/- 2.6% of current amplitude through the CaV1.2b channel and 28.0 +/- 2.7% of current through the CaV1.2a channel. Inhibition was not accompanied by alteration of current waveform or by shift of current-voltage relation. In a current clamp haloperidol suppressed action potential generation. 1 micromol/l of the drug shortened the action potential duration in part of the cells and suppressed fully action potential in other cells. Moderate inhibition of the L-type calcium channels by haloperidol might cause shortening of action potential. Complete abolishment of action potential must have been mediated by inhibition of another, likely sodium channel.
Tarabová
Bohumila
B
Institute of Molecular Physiology and Genetics, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovakia.
Nováková
Marie
M
Lacinová
L'ubica
L
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D020033:Protein Isoforms; C493217:calcium channel, l type beta2c subunit, rat; D006220:Haloperidol; D002118:Calcium