Brief Article
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World J Gastroenterol. Jan 28, 2012; 18(4): 356-367
Published online Jan 28, 2012. doi: 10.3748/wjg.v18.i4.356
Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats
Li-Jie Pan, Zi-Chao Zhang, Zhen-Ya Zhang, Wen-Jun Wang, Yue Xu, Zong-Ming Zhang
Li-Jie Pan, Zi-Chao Zhang, Zhen-Ya Zhang, Zong-Ming Zhang, Department of General Surgery, Digestive Medical Center, The First Affiliated Hospital, School of Medicine, Tsinghua University, Beijing 100016, China
Wen-Jun Wang, Yue Xu, Xuyue (Beijing) Science and Technology Co., Ltd., Haidian District, Beijing 100080, China
Author contributions: Pan LJ and Zhang ZM designed the research and wrote the paper; Pan LJ, Zhang ZC, Zhang ZY and Wang WJ performed the main research; Xu Y and Zhang ZM provided the research tools.
Supported by The National Natural Science Foundation of China, No. 30670744 and 81071996; Tsinghua-Yue-Yuen Medical Science Foundation, No. 20240000531 and 20240000547
Correspondence to: Zong-Ming Zhang, MD, PhD, Professor, Department of General Surgery, Digestive Medical Center, The First Affiliated Hospital, School of Medicine, Tsinghua University, Beijing 100016, China. zhangzongming@mail.tsinghua.edu.cn
Telephone: +86-10-64372362 Fax: +86-10-64361322
Received: May 3, 2011
Revised: July 18, 2011
Accepted: July 25, 2011
Published online: January 28, 2012
Abstract

AIM: To further investigate the important role of store-operated calcium channels (SOCs) in rat hepatocytes and to explore the effects of SOC blockers on hepatic ischemia-reperfusion injury (HIRI).

METHODS: Using freshly isolated hepatocytes from a rat model of HIRI (and controls), we measured cytosolic free Ca2+ concentration (by calcium imaging), net Ca2+ fluxes (by a non-invasive micro-test technique), the SOC current (ISOC; by whole-cell patch-clamp recording), and taurocholate secretion [by high-performance liquid chromatography and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays].

RESULTS: Ca2+ oscillations and net Ca2+ fluxes mediated by Ca2+ entry via SOCs were observed in rat hepatocytes. ISOC was significantly higher in HIRI groups than in controls (57.0 ± 7.5 pA vs 31.6 ± 2.7 pA, P < 0.05) and was inhibited by La3+. Taurocholate secretion by hepatocytes into culture supernatant was distinctly lower in HIRI hepatocytes than in controls, an effect reversed by SOC blockers.

CONCLUSION: SOCs are pivotal in HIRI. SOC blockers protected against HIRI and assisted the recovery of secretory function in hepatocytes. Thus, they are likely to become a novel class of effective drugs for prevention or therapy of HIRI patients in the future.

Keywords: Hepatocyte, Hepatic ischemia-reperfusion injury, Store-operated calcium channel, Non-invasive micro-test technique