Regulation of total mitochondrial Ca2+ in perfused liver is independent of the permeability transition pore

Helsinki Biophysics and Biomembranes Group, Department of Medical Chemistry, Institute of Biomedicine, FIN-00014 University of Helsinki, Helsinki, Finland Triggering of the permeability transition pore (PTP) in isolated mitochondria causes release of matrix Ca 2+ , ions, and metabolites, and it has been proposed that the PTP mediates mitochondrial Ca 2+ release in intact cells. To study the role of the PTP in mitochondrial energy metabolism, the mitochondrial content of Ca 2+ , Mg 2+ , ATP, and ADP was determined in hormonally stimulated rat livers perfused with cyclosporin A (CsA). Stimulation of livers perfused in the absence of CsA with glucagon and phenylephrine induced an extensive uptake of Ca 2+ , Mg 2+ , and ATP plus ADP by the mitochondria, followed by a release on omission of hormones. In the presence of CsA, the PTP was fully inhibited, but neither the hormone-induced uptake of Ca 2+ , ATP, or ADP by mitochondria nor their release after washout of hormones was significantly changed. We conclude that the regulation of sustained changes in mitochondrial Ca 2+ content induced by hormonal stimulation is independent of the PTP. cyclosporin A; permeability transition; mitochondria; calcium; intact rat liver