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 DNP-stimulated respiration, or swelling in K+ salt in the presence of valinomycin. 3. The inhibitory concentration of Ni2+ dependent 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.