Inhibition by Sr2+ of specific mitochondrial Ca2+-efflux pathways.

The effect of Sr2+ on the set point for external Ca2+ was studied in rat heart and liver mitochondria with the aid of a Ca2+-sensitive electrode. In respiring mitochondria the set point is determined by the rates of Ca2+ influx on the Ca2+ uniporter and efflux by various mechanisms. We studied the Ca2+-Na+ exchange pathway in heart mitochondria and the delta psi-modulated efflux pathway in liver mitochondria. Prior accumulation of Sr2+ was found to shift the set points towards lower external Ca2+ both in heart mitochondria under conditions of Ca2+-Na+ exchange and in liver mitochondria under conditions that should promote opening of the delta psi-modulated pathway. The effect on the set point was found to be due to inhibition of Ca2+ efflux by Sr2+ taken up by the mitochondria, while Sr2+ efflux was too slow to be measurable.