title: Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats.
abstract: OBJECTIVE
  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 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].
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Surgery, Digestive Medical Center, The First Affiliated Hospital, School of Medicine, Tsinghua University, Beijing 100016, China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Pan
authors.forename: Zi-Chao
authors.initials: ZC
authors.lastname: Zhang
authors.forename: Zhen-Ya
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.forename: Zong-Ming
authors.initials: ZM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013656:Taurocholic Acid / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002756:Cholagogues and Choleretics; D013656:Taurocholic Acid; D002118:Calcium; D009638:Norepinephrine