Effects of Haloperidol on Ca2+i Change in HIT T-15 Insulinoma Cells.
- Author:
Min Hyuk KIM
1
;
Ki Chang PARK
;
Se Young JIN
;
Dae Ran KIM
;
Min Jeong KIM
;
Kyu Sang PARK
;
In Deok KONG
Author Information
1. Department of Psychiatry, Aerospace Medical Center, Chungju, Korea.
- Publication Type:Original Article
- Keywords:
Haloperidol;
HIT T-15 cell;
[Ca2+]i;
Sigma receptor
- MeSH:
Animals;
Calcium;
Cricetinae;
Diabetes Mellitus;
Haloperidol*;
Insulinoma*;
KATP Channels;
Membrane Potentials;
Receptors, sigma
- From:Korean Journal of Psychopharmacology
2007;18(5):288-298
- CountryRepublic of Korea
- Language:Korean
-
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.
