Mitochondrial cation-hydrogen ion exchange. Sodium selective transport by mitochondria and submitochondrial particles.

The neutral exchange between Na+ or K+ ions and protons across the mitochondrial membrane was studied by means of passive swelling in isotonic acetate salts. The selectivity for Na+ over K+ was approximately 50: 1. The rate of Na+-dependent swelling mediated by the natural exchange system was sensitive to pH and inhibited 70% or more by 20 rnM Mgr+. Physiological Mg 2+ levels, however, inhibited only about 15 %. According to direct flux measurements with submitochondrial particles, the endogenous cation-H+ exchange possessed an apparent Na+:K+ selectivity ranging from 6 to 1O:l depending upon the experimental conditions. These ratios were found to be underestimates of the actual selectivity due to translocation of endogenous Na+ ions. Values corrected accordingly were comparable to those obtained for intact mitochondria. Natural mitochondrial cation-H+ exchange was compared to exchange mediated by the “ionophore,” nigericin. Kinetic studies with mitochondria and submitochondrial particles yielded a Na+ :K+ selectivity ratio of 1.0 for nigericin. Cation discrimination was the major difference between endogenous and nigericin-dependent exchange. Differences between properties of ionophores in model systems and their kinetic behavior in biological membranes are discussed in the context of isolation-reconstitution studies.