EVIDENCE FOR MITOCHONDRIAL CA2-INDUCED CA2+ RELEASE IN PERMEABILIZED ENDOTHELIAL-CELLS()

Generally most intracellular Ca2+ is stored in the endoplasmic reticul um (ER) and mitochondria, Recently a mitochondrial Ca2+-induced Ca2+ r elease (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-permea bilised BAE cells. When buffered intracellular solutions were 'stepped ' from 10 nM to 10 mu M free Ca2+, the mitochondrial inhibitors CN (2 mM), FCCP (1 mu M), and RR (20 mu M) significantly reduced total CICR by approximately 25%. The ER Ca2+-ATPase inhibitor thapsigargin (100 n M) 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 mechan ism previously reported in BAE cells involves mitochondrial Ca2+ relea se. It is proposed that in BAE cells, mCICR occurs via the mitochondri al PTP and may be physiologically important in endothelial cell Ca2+ s ignalling. (C) 1998 Academic Press.