Respiration-dependent contraction of swollen heart mitochondria: participation of the K+/H+ antiporter.
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.
Brierley
G P
GP
Department of Physiological Chemistry, Ohio State University Medical Center, Columbus 43210.
Davis
M H
MH
Jung
D W
DW
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D010101:Oxygen Consumption; D010539:Permeability; D011188:Potassium / Q000378:metabolism*; D017680:Potassium Compounds; D027961:Potassium-Hydrogen Antiporters
D002352:Carrier Proteins; D009566:Nitrates; D017680:Potassium Compounds; D027961:Potassium-Hydrogen Antiporters; D004024:Dicyclohexylcarbodiimide; D006859:Hydrogen; D008274:Magnesium; C023844:potassium nitrate; D011188:Potassium