Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats

Abstract

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). Using freshly isolated hepatocytes from a rat model of HIRI (and controls), we measured cytosolic 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 recording), and taurocholate secretion [by high-performance liquid chromatography and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays]. Ca(2+) oscillations and net Ca(2+) fluxes mediated by Ca(2+) entry via SOCs were observed in rat hepatocytes. 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. 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.