On the mechanism of rebounding of calcium in liver mitochondria.

Rat liver mitochondria are able to temporarily lower the steady state concentration of external Ca2+ after having accumulated a pulse of added Ca2+. This could be due to inhibition of efflux or/and stimulation of influx of Ca2+. This question has been addressed in mitochondria respiring on succinate +/- malonate. In the presence of malonate the depression of the membrane potential during Ca2+ uptake is more extensive and the rate of Ca2+ uptake slower. There were no discernible differences in the rates of efflux either after inhibition of the calcium uniporter by Ruthenium Red or by studying efflux of preloaded 45Ca-labeled Ca2+. The efflux was not changed by diltiazem or cyclosporin A to inhibit Ca2+ exchange on the Ca2+/nNA+ antiporter or efflux through the permeability transition pore. It is concluded that the rebounding is due mainly to stimulation of the calcium uniporter.