Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 7, 2006; 12(29): 4694-4698
Published online Aug 7, 2006. doi: 10.3748/wjg.v12.i29.4694
Effects of Ca2+ channel blockers on store-operated Ca2+ channel currents of Kupffer cells after hepatic ischemia/reperfusion injury in rats
Nan Jiang, Zong-Ming Zhang, Liang Liu, Chi Zhang, Yan-Lu Zhang, Zi-Chao Zhang
Nan Jiang, Zong-Ming Zhang, Department of General Surgery, Digestive Medical Center, First Affiliated Hospital of Tsinghua University, Beijing 100016, China
Liang Liu, Chi Zhang, Yan-Lu Zhang, Zi-Chao Zhang, Department of 1st General Surgery of Tongji Hospital, Tongji University, Shanghai 200065, China
Supported by the National Natural Science Foundation of China, No.30270532; Trans-Century Training Programme Foundation for the Talents by the Ministry of Education of China, No. 2002-48; Shuguang Program Project of Shanghai Educational Committee, No.02SG20
Correspondence to: Professor Zong-Ming Zhang, Department of General Surgery, Digestive Medical Center, First Affiliated Hospital of Tsinghua University, Beijing 100016, China. zhangzongming@mail.tsinghua.edu.cn
Telephone: +86-10-64372362 Fax: +86-10-64361322
Received: January 12, 2006
Revised: January 28, 2006
Accepted: February 18, 2006
Published online: August 7, 2006
Abstract

AIM: To study the effects of hepatic ischemia/reperfusion (I/R) injury on store-operated calcium channel (SOC) currents (ISOC) in freshly isolated rat Kupffer cells, and the effects of Ca2+ channel blockers, 2-aminoethoxydiphenyl borate (2-APB), SK&F96365, econazole and miconazole, on ISOC in isolated rat Kupffer cells after hepatic I/R injury.

METHODS: The model of rat hepatic I/R injury was established. Whole-cell patch-clamp techniques were performed to investigate the effects of 2-APB, SK&F96365, econazole and miconazole on ISOC in isolated rat Kupffer cells after hepatic I /R injury.

RESULTS: I/R injury significantly increased ISOC from -80.4 ± 25.2pA to -159.5 ± 34.5pA (bP < 0.01, n = 30). 2-APB (20, 40, 60, 80, 100 μmol/L), SK&F96365 (5, 10, 20, 40, 50 μmol/L), econazole (0.1, 0.3, 1, 3, 10 μmol/L) and miconazole (0.1, 0.3, 1, 3, 10 μmol/L) inhibited ISOC in a concentration-dependent manner with IC50 of 37.41 μmol/L (n = 8), 5.89 μmol/L (n = 11), 0.21 μmol/L (n = 13), and 0.28 μmol/L (n = 10). The peak value of ISOC in the I-V relationship was decreased by the blockers in different concentrations, but the reverse potential of ISOC was not transformed.

CONCLUSION: SOC is the main channel for the influx of Ca2+ during hepatic I/R injuries. Calcium channel blockers, 2-APB, SK&F96365, econazole and miconazole, have obviously protective effects on I/R injury, probably by inhibiting Isoc in Kupffer cells and preventing the activation of Kupffer cells.

Keywords: Kupffer cell, Ischemia/reperfusion, Store-operated calcium channel currents, 2-aminoethoxydiphenyl borate, SK&F96365, Econazole, Miconazole