Respiration-dependent contraction of swollen heart mitochondria: participation of the K+/H+ antiporter

Abstract

Respiration-dependent contraction of heart mitochondria swollen passively in K+ nitrate is activated by the ionophore A23187 and inhibited by Mg2+. Ion extrusion and osmotic contraction under these conditions are strongly inhibited by quinine, a known inhibitor of the mitochondrial K+/H+ antiporter, as measured in other systems. The inhibition by quinine is relieved by the exogenous antiporter nigericin. Respiration-dependent contraction is also inhibited by dicyclohexylcarbodiimide (DCCD) when reacted under conditions known to inhibit K+/H+ antiport (Martin et al., J. Biol. Chem. 259, 2062-2065, 1984). These studies strongly support the concept that K+ is extruded from the matrix by the endogenous K+/H+ antiporter and that inhibition of this component by quinine or DCCD inhibits respiration-dependent contraction. The extrusion of K+ nitrate is accompanied by a respiration-dependent efflux of a considerable portion of the endogenous Mg2+. This Mg2+ efflux does not occur in the presence of nigericin or when the mitochondrial Na+/H+ antiporter is active. Mg2+ efflux may take place on the K+/H+ antiporter. DCCD, reacted under conditions that do not result in inhibition of the K+/H+ antiporter, blocks a monovalent cation uniport pathway. This uniport contributes to futile cation cycling at elevated pH, and its inhibition by DCCD stimulates respiration-dependent contraction.