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

Triggering ofthe permeability transition pore (PTP) in isolated mitochondria causesrelease of matrix Ca²⁺, ions, andmetabolites, and it has been proposed that the PTP mediatesmitochondrial Ca²⁺ release inintact cells. To study the role of the PTP in mitochondrial energymetabolism, the mitochondrial content ofCa²⁺,Mg²⁺, ATP, and ADP was determinedin hormonally stimulated rat livers perfused with cyclosporin A (CsA).Stimulation of livers perfused in the absence of CsA with glucagon andphenylephrine induced an extensive uptake ofCa²⁺,Mg²⁺, and ATP plus ADP by themitochondria, followed by a release on omission of hormones. In thepresence of CsA, the PTP was fully inhibited, but neither thehormone-induced uptake of Ca²⁺,ATP, or ADP by mitochondria nor their release after washout of hormoneswas significantly changed. We conclude that the regulation of sustainedchanges in mitochondrial Ca²⁺content induced by hormonal stimulation is independent of the PTP.