Alterations in intracellular calcium compartmentation following inhibition of calcium efflux from isolated hepatocytes.
Addition of ATP to the incubation medium of freshly isolated rat hepatocytes causes a marked inhibition of the efflux of Ca2+ from the cells, and its accumulation in intracellular compartments. After an initial rise in cytosolic free Ca2+ concentration, as indicated by the activation of phosphorylase, Ca2+ is preferentially sequestered in the mitochondria, without any apparent contribution by the endoplasmic reticulum. Impairment of mitochondrial Ca2+ homeostasis by pyridine nucleotide oxidation associated with tert-butyl hydroperoxide metabolism, prevents the ATP-dependent cellular Ca2+ accumulation and causes a release of Ca2+ from the hepatocytes into the medium. Conversely, maintenance of the mitochondrial pyridine nucleotides in a more reduced state, e. g. in presence of 3-hydroxybutyrate in the medium, prevents this hydroperoxide-induced release of intracellular Ca2+. Under conditions of impaired mitochondrial Ca2+ sequestration, there appears to be a redistribution of a minor fraction of the intracellular Ca2+ from the mitochondria to the endoplasmic reticulum. Our results provide additional evidence for the critical involvement of the plasma membrane Ca2+-extruding system in the physiological regulation of the cytosolic free Ca2+ concentration in hepatocytes, and suggest that the mitochondria play a more important role than the endoplasmic reticulum in the regulation of the cytosolic free Ca2+ level when the plasma membrane Ca2+ pump is inhibited.
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D020122:tert-Butylhydroperoxide
D007473:Ion Channels; D010545:Peroxides; D000255:Adenosine Triphosphate; D020122:tert-Butylhydroperoxide; D002118:Calcium