CA2+ RELEASE FROM MITOCHONDRIA INDUCES CYTOSOLIC ENZYME LEAKAGE IN ANOXIC LIVER

The mechanisms of elevation of cytosolic Ca2+ concentration during ano xia causing cytosolic enzyme leakage were studied in perfused rat live r. Before anoxia the Ca2+ contents in mitochondria of perfused rat liv er were varied by addition of noradrenaline and glucagon, lowering Ca2 + concentration in the perfusion medium, and addition of Ca2+ channel blocker, either singly or in combination. The amount of cytosolic enzy me leakage during anoxic perfusion positively correlated with the mito chondrial Ca2+ content just before anoxia and also with Ca2+ release f rom mitochondria during anoxia. However, the amount of cytosolic enzym e leakage during anoxic perfusion did not correlate with the Ca2+ conc entration in the perfusion medium and microsomal Ca2+ content. These d ata support the hypothesis that in anoxic liver, the cytosolic Ca2+ co ncentration is elevated to a pathological level mainly by Ca2+ release from mitochondria, causing the cytosolic enzyme leakage. (C) 1995 Aca demic Press, Inc.