Haloperidol blocks voltage-activated Ca2+ channels in hippocampal neurones.
The Ca2+ channel antagonist action of the antipsychotic haloperidol was investigated using two functional assays of Ca2+ channel activity. Haloperidol dose dependently attenuated the rise in intracellular free Ca2+ ([Ca2+]i) evoked by 50 mM extracellular K+ in Fura-2 loaded cultured rat hippocampal neurones with an IC50 (+/- S.E.M.) of 7.8 +/- 0.5 microM and similarly reduced whole-cell Ba2+ currents (IBa) in voltage-clamped mouse hippocampal neurones with an IC50 value of 15.6 +/- 1.1 microM. Block of whole-cell IBa by haloperidol was rapid, fully reversible, and was greater at more depolarized membrane potentials. Our data indicate that haloperidol non-selectively blocks neuronal voltage-gated Ca2+ channels at micromolar concentrations.
Fletcher
E J
EJ
Department of Physiology, University of Toronto, Ont., Canada.
Church
J
J
MacDonald
J F
JF
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004594:Electrophysiology; D005456:Fluorescent Dyes; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats
D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D001464:Barium; D006220:Haloperidol; D011188:Potassium