A gated pathway for electrophoretic Na⁺ fluxes in rat liver mitochondria

Addition of EDTA to mitochondria incubated aerobically in a phosphate-supplemented medium containing Na+ ions results in activation of cation uptake which is accompanied by membrane depolarization and stimulation of respiration. The same results are obtained in media containing Li+ but not K+, indicating that this pathway for cation transport is selective. The activation of Na+ transport is not accompanied by changes of matrix Mg2+, indicating that cation transport is controlled by surface-bound rather than intramitochondrial Mg2+. Na+ transport in respiring mitochondria is competitively inhibited by Mg2+ with a Ki in the nanomolar range. A Na+ current can also be induced by a K+ diffusion potential in the absence of respiration. The K(+)-diffusion-driven Na+ current has the same magnitude in the absence or presence of inorganic phosphate, suggesting that Na+ transport is mediated by Na+ uniport rather than by electrogenic nNa+/H+ antiport with n greater than 1. Analysis of the flow/force relationship indicates that the putative Na+ uniporter has a conductance of about 0.2 nmol Na+ x mg protein-1 x min-1 x mV-1, and that it is active only when the membrane potential exceeds about 150 mV.