Ni2+, a new inhibitor of mitochondrial calcium transport

1. The effect of Ni²⁺ on respiration, volume changes and Ca²⁺ movements was investigated in rat liver mitochondria. 2. Ni²⁺ inhibited Ca²⁺ uptake into respiring mitochondria, Ca²⁺-stimulated respiration and swelling in Ca²⁺ salts, whereas it did not inhibit either state 4 and NDP-stimulated respiration, or swelling in K⁺ salt in the presence of valinomycin. 3. The inhibitory concentration of Ni²⁺ depended strongly on the applied Ca²⁺ concentration. As revealed by direct methods, 50% inhibition of Ca²⁺ influx was achieved by approx. 2-fold excess of Ni²⁺. 4. If added to Ca²⁺-loaded mitochondria, Ni²⁺ gave rise to slow Ca²⁺ release and inhibited uncoupler-induced efflux slightly. 5. It is concluded that Ni²⁺ is a potent inhibitor of mitochondrial Ca²⁺ transport. Ca²⁺ influx is far more sensitive to inhibition than Ca²⁺ efflux.