title: Evidence for mitochondrial Ca(2+)-induced Ca2+ release in permeabilised endothelial cells.
abstract: Generally most intracellular Ca2+ is stored in the endoplasmic reticulum (ER) and mitochondria. Recently a mitochondrial Ca(2+)-induced Ca2+ release (mCICR) mechanism, unconnected with ryanodine receptors (RyR's), has been shown in tumour cells. The existence of a mitochondrial Ca2+ release mechanism in BAE cells was investigated using saponin-permeabilised BAE cells. When buffered intracellular solution were 'stepped' from 10 nM to 10 microM free Ca2+, the mitochondrial inhibitors CN (2 mM), FCCP (1 microM), and RR (20 microM) significantly reduced total CICR by approximately 25%. The ER Ca(2+)-ATPase inhibitor thapsigargin (100 nM) had no effect. Furthermore, cyclosporin A (200 nM), an inhibitor of the mitochondrial permeability transition pore (PTP), abolished total CICR. Therefore, the novel ryanodine-caffeine insensitive CICR mechanism previously reported in BAE cells involves mitochondrial Ca2 release. It is proposed that in BAE cells, mCICR occurs via the mitochondrial PTP and may be physiologically important in endothelial cell Ca2+ signalling.
authors.affiliation: Department of Physiological Sciences, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom. P.G.Wood@newcastle.ac.uk
authors.forename: P G
authors.initials: PG
authors.lastname: Wood
authors.forename: J I
authors.initials: JI
authors.lastname: Gillespie
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003486:Cyanides / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010539:Permeability; D012430:Ruthenium Red / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D003486:Cyanides; D012430:Ruthenium Red; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D019284:Thapsigargin; D016572:Cyclosporine; D002118:Calcium