N-n-Butyl Haloperidol Iodide Preserves Cardiomyocyte Calcium Homeostasis during Hypoxia/Ischemia

Cellular Physiology and Biochemistry

关键词: N-n-Butyl haloperidol iodide;    Calcium transients;    Ventricular myocytes;    Hypoxia/ischemia;   

DOI  :  10.1159/000329964

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Aims N-n-Butyl haloperidol iodide (F₂) is a novel compound derived from haloperidol. In our previous work, F₂ was found to be an L-type calcium channel blocker which played a protective role in rat heart ischemic–reperfusion injury in a dose-dependent manner. In the current study, we aimed to investigate the effects and some possible mechanisms of F₂ on calcium transients in hypoxic/ischemic rat cardiac myocytes. Methods and Results Calcium transients’ images of rat cardiac myocytes were recorded during simulated hypoxia, using a confocal calcium imaging system. The amplitude, rising time from 25% to 75% (RT25-75), decay time from 75% to 25% (DT75-25) of calcium transients, and resting [Ca²⁺]_i were extracted from the images by self-coding programs. In this study, hypoxia produced a substantial increase in diastolic [Ca²⁺]_i and reduced the amplitude of calcium transients. Both RT25-75 and DT75-25 of Ca²⁺ transients were significantly prolonged. And F₂ could reduce the increase in resting [Ca²⁺]_iand the prolongation of RT25-75 and DT75-25 of Ca²⁺ transients during hypoxia. F₂ also inhibited the reduction in amplitude of calcium transients which was caused by 30-min hypoxia. The activity of SERCA2a (sarcoplasmic reticulum Ca²⁺-ATPase, determined by test kits) decreased after 30-min ischemia, and intravenous F₂ in rats could ameliorate the decreased activity of SERCA2a. The inward and outward currents of NCX (recorded by whole-cell patch-clamp analysis) were reduced during 10-min hypoxia, and F₂ further inhibited the outward currents of NCX during 10-min hypoxia. All these data of SERCA2a and NCX might be responsible for the changes in calcium transients during hypoxia. Conclusion Our data suggest that F₂ reduced changes in calcium transients that caused by hypoxia/ischemia, which was regarded to be a protective role in calcium homeostasis of ventricular myocytes, probably via changing the function of SERCA2a.

【 授权许可】

CC BY-NC-ND