Effects of quinine on K+ transport in heart mitochondria

Quinine inhibits the respiration-dependent extrusion of K+ from Mg2+-depleted heart mitochondria and the passive osmotic swelling of these mitochondria in K+ and Na+ acetate at alkaline pH. These observations concur with those of Nakashima and Garlid (J. Biol. Chem. 257, 9252, 1982) using rat liver mitochondria. Quinine also inhibits the respiration-dependent contraction of heart mitochondria swollen passively in Na+ or K+ nitrate and the increment of elevated respiration associated with the extrusion of ions from these mitochondria. Quinine, at concentrations up to 0.5 mM, inhibits the respiration-dependent 42K+/K+ exchange seen in the presence of mersalyl, but higher levels of the drug produce increased membrane permeability and net K+ loss from the matrix. These results are all consistent with an inhibition of the putative mitochondrial K+/H+ antiport by quinine. However, quinine has other effects on the mitochondrial membrane, and possible alternatives to this interpretation are discussed.