Evidence that glucagon acts on the liver to decrease mitochondrial calcium stores.

1. Mitochondria isolated from rats treated with glucagon for 60 min or lives perfused in the presence of glucagon for 10 min exhibited lower rates of 45Ca2+ exchange than did control mitochondria when this was measured under steady-state conditions in the presence of Mg2+, ATP, Pi and 0.13 microM- or 0.16 microM-free Ca2+ at pH 7.4 and at 25 degrees C or 37 degrees C. Under these conditions no significant difference in the rates of Ruthenium Red-induced 45Ca2+ efflux was observed. These results contrast with earlier work in which mitochondria isolated from glucagon-treated livers were shown to exhibit faster rates of Ca2+ uptake [Yamazaki (1975) J. Biol. Chem. 250, 7924-7930] and slower rates of spontaneous Ca2+ efflux [Hughes & Barritt (1978) Biochem. J. 176, 295-304] when these parameters were measured under different incubation conditions, including supra-physiological concentrations of free Ca2+ and the absence of added Mg2+ and ATP. 2. Perfusion of livers with glucagon before the addition of adrenaline or the Ca2+-selective ionophore A23187, to release Ca2+ from intracellular stores, decreased the amount of Ca2+ released by these agents. 3. Incubation of isolated hepatocytes in the presence of glucagon at 1.3 mM extracellular Ca2+ induced a small decrease in the plateau of the 45Ca2+-exchange curve obtained under steady-state conditions. 4. It is concluded that the actions of glucagon on liver mitochondrial Ca2+ transporters lead to a decrease, rather than an increase, in mitochondrial Ca2+ stores in the intact cell.