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...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 cyto-solic free Ca 2+ concentration (by calcium imaging),net Ca 2+ fluxes (by a non-invasive micro-test technique),the SOC current (I SOC ;by whole-cell patch-clamp record-ing),and taurocholate secretion [by high-performance liquid chromatography and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays].RESULTS:Ca 2+ oscillations and net Ca 2+ fluxes medi-ated by Ca 2+ entry via SOCs were observed in rat he-patocytes.I SOC 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 La 3+.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 se-cretory 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.展开更多
基金Supported by The National Natural Science Foundation ofChina,No.30670744and81071996Tsinghua-Yue-Yuen Medical Science Foundation,No.20240000531and20240000547
文摘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 cyto-solic free Ca 2+ concentration (by calcium imaging),net Ca 2+ fluxes (by a non-invasive micro-test technique),the SOC current (I SOC ;by whole-cell patch-clamp record-ing),and taurocholate secretion [by high-performance liquid chromatography and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays].RESULTS:Ca 2+ oscillations and net Ca 2+ fluxes medi-ated by Ca 2+ entry via SOCs were observed in rat he-patocytes.I SOC 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 La 3+.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 se-cretory 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.
