Quinine inhibition of Na+ and K+ transport provides evidence for two cation/H+ exchangers in rat liver mitochondria.

K+ efflux from respiring mitochondria via the K+/H+ exchanger is inhibited by quinine. In contrast, swelling in fresh mitochondria suspended in Na+ acetate, reflecting activity of the Na+/H+ exchanger, is unaffected by quinine. Swelling studies were also carried out in K+ and Na+ acetate in mitochondria loaded with tetraethylammonium and depleted of Mg2+ and K+. From the effects of pH and quinine on this preparation, we conclude that there are two distinct electroneutral pathways for monovalent cations. The Na+/H+ exchanger is highly specific for Na+ over K+ and is neither regulated by Mg2+ ions nor inhibited by quinine. The K+/H+ exchanger transports both Na+ and K+ and is regulated by Mg2+ ions and inhibited by quinine.