Regulation of total mitochondrial Ca2+ in perfused liver is independent of the permeability transition pore.
Triggering of the permeability transition pore (PTP) in isolated mitochondria causes release of matrix Ca2+, ions, and metabolites, and it has been proposed that the PTP mediates mitochondrial Ca2+ release in intact cells. To study the role of the PTP in mitochondrial energy metabolism, the mitochondrial content of Ca2+, Mg2+, 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 Ca2+, Mg2+, 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 Ca2+, 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 Ca2+ content induced by hormonal stimulation is independent of the PTP.
Eriksson
O
O
Helsinki Biophysics and Biomembranes Group, Department of Medical Chemistry, Institute of Biomedicine, FIN-00014 University of Helsinki, Helsinki, Finland. ove.eriksson@helsinki.fi
Pollesello
P
P
Geimonen
E
E
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010477:Perfusion; D010539:Permeability; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D007166:Immunosuppressive Agents; D010656:Phenylephrine; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D005934:Glucagon; D008274:Magnesium; D002118:Calcium