Effects of N-n-butyl haloperidol iodide on L-type calcium channels and intracellular free calcium in rat ventricular myocytesThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.

Abstract

The ability of N-n-butyl haloperidol iodide (F2) to cause vasodilation, and thereby produce a cardioprotective effect, has been well documented. The aim of this study was to investigate whether F2 might act as a Ca2+ antagonist. Myocytes were obtained from rat heart, and the whole-cell patch-clamp technique was used to record Ca2+ current. Laser scanning confocal microscopy was used to measure intracellular free calcium ([Ca2+]i). The results obtained from this study demonstrate that F2 reduced calcium current (ICa) in a concentration-dependent manner with an IC50 of 1.19 micromol/L, upshifted the current-voltage curve of ICa, shifted the inactivation kinetics of ICa leftward, and slowed down the recovery of ICa from inactivation. F2 decreased the fluorescent intensity of [Ca2+]i elevation induced by KCl with an IC50 of 1.61 micromol/L, and had no effects on the intracellular calcium release induced by caffeine and inositol-1,4,5-trisphosphate. These findings indicate that F2 may act as a calcium antagonist, which could account for its cardiovascular benefits.

Haloperidol moderately inhibits cardiovascular L-type calcium current

“…In most experiments, including those reported here, the inhibition of calcium current was reversible upon washout (Fletcher et al 1994;Ito et al 1996;Huang et al 2003Huang et al , 2007. Recovery of calcium current amplitude upon washout was more effective in HEK 293 cells expressing recombinant Ca V 1.2 channels and in PC12 cells than in cardiomyocytes.…”

“…1 μmol/l of F 2 inhibited more than 70% of L-type calcium current amplitude in rat ventricular myocytes independent of the amplitude of depolarizing pulse (Huang et al 2003(Huang et al , 2007. This drug was moderately more effective calcium channel blocker than haloperidol.…”

“…PC12 cells (Ito et al 1996). Huang et al (2003Huang et al ( , 2007 used rat cardiac myocytes in their experiments, nevertheless, instead of haloperidol they used its quaternary ammonium salt derivative with different chemical properties.…”

N-n-butyl haloperidol iodide inhibits H2O2- induced Na+/Ca2+-exchanger activation via the Na+/H+ exchanger in rat ventricular myocytes

“…Our previous studies show that F 2 can attenuate myocardial I/R injury, as evidenced by amelioration of hemodynamics and myocardial enzyme activity, reduction in myocardial infarction size, prevention of ventricular arrhythmias, and decreases in myocardial inflammation 11–14. The cardioprotective mechanism of F 2 was thought to be associated with calcium-homeostasis maintenance against intracellular Ca 2+ overload by inhibiting cardiocyte L-type Ca 2+ channels 12,13. However, intracellular Ca 2+ overload during I/R results primarily from the functional coupling of NHE and NCX.…”

Guattegaumerine Protects Primary Cultured Cortical Neurons Against Oxidative Stress Injury Induced by Hydrogen Peroxide Concomitant with Serum Deprivation

“…can increase [Ca 2? ] i by activation of voltage-dependent calcium channel (VDCC)(Huang et al 2007). VDCC activation contributes a depolarizing current by allowing calcium influx.…”