Korean J Psychopharmacol.  2007 Sep;18(5):288-298.

Effects of Haloperidol on [Ca2+]i Change in HIT T-15 Insulinoma Cells

• Kim MH
• Park KC
• Jin SY
• Kim DR
• Kim MJ
• Park KS
• Kong ID

Abstract

OBJECTIVE
The purpose of this study was to investigate the effects of haloperidol on [Ca2+]i in hamster insulinoma cells (HIT T-15).
METHODS
[Ca2+]i levels were measured by calcium imaging techniques, and membrane potential ionic currents were recorded using conventional patch-clamp methods.
RESULTS
Haloperidol induced a transient [Ca2+]i increase, which was abolished by the removal of extracellular Ca2+ or pretreatment with Ca2+ channel blockers (nimodipine and mibefradil). Haloperidol depolarized the membrane potential and inhibited the ATP-sensitive K+ (KATP) channels. Sigma receptor agonists, (+)-SKF10047 and ifenprodil, induced a transient [Ca2+]i increase similar to haloperidol. BD1047, a sigma receptor antagonist, completely blocked the [Ca2+]i increase induced by haloperidol. Haloperidol inhibited the KCl-induced [Ca2+]i increase and voltage-dependent Ca2+ currents. Sigma receptor agonists [(+)-SKF10047, ifenprodil] also inhibited the KCl-induced [Ca2+]i increase.
CONCLUSION
Our results suggest that haloperidol induces depolarization, which increases [Ca2+]i by voltage-gated Ca2+ currents via the closing of KATP channels. Haloperidol also inhibits KCl-induced [Ca2+]i increases in the same manner. These effects of haloperidol seemed to be mediated by sigma receptors, which might be linked to the pathogenesis of haloperidol-induced diabetes mellitus.

Keyword

Haloperidol; HIT T-15 cell; [Ca2+]i; Sigma receptor

MeSH Terms

Animals
Calcium
Cricetinae
Diabetes Mellitus
Haloperidol*
Insulinoma*
KATP Channels
Membrane Potentials
Receptors, sigma
Calcium
Haloperidol
KATP Channels
Receptors, sigma