On the mechanism by which dicyclohexylcarbodiimide and quinine inhibit K+ transport in rat liver mitochondria.
Passive uptake of potassium acetate into the mitochondrial matrix can be induced by nigericin, a K+/H+ antiporter, or by A23187, a Mg2+/2H+ antiporter. The latter process is thought to reflect operation of the Mg2+-dependent, endogenous K+/H+ antiporter, but there is ambiguity with respect to the mechanism of K+ transport in this assay (Nakashima, R.A., and Garlid, K.D. (1982) J. Biol. Chem. 257, 9252-9254). Kinetic analysis of potassium acetate transport provides verification that Mg2+ depletion 1) unmasks the K+/H+ antiporter, 2) opens up an intrinsic anion uniporter, 3) has no effect on acetic acid transport, and 4) does not induce high K+ uniport conductance. Mg2+-dependent uptake of potassium acetate is thereby shown to be mediated specifically by operation of the endogenous K+/H+ antiporter, as previously proposed. An extension of this analysis confirms that N,N'-dicyclohexylcarbodiimide and quinine block potassium acetate uptake via specific action on the K+/H+ antiporter. These findings support those of a previous study (Martin, W.H., Beavis, A.D., and Garlid, K.D. (1984) J. Biol. Chem. 259, 2062-2065) in which binding of [14C]N,N'-dicyclohexylcarbodiimide to membrane proteins under selective conditions was used to identify an 82,000-dalton band as the protein responsible for K+/H+ antiport in mitochondria.
D000085:Acetates / Q000378:metabolism*; D019342:Acetic Acid; D000818:Animals; D027321:Anion Transport Proteins; D001692:Biological Transport / Q000187:drug effects; D002234:Carbodiimides / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009550:Nigericin / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D017680:Potassium Compounds; D027961:Potassium-Hydrogen Antiporters; D011796:Quinacrine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology*; D051381:Rats
D000085:Acetates; D027321:Anion Transport Proteins; D002234:Carbodiimides; D002352:Carrier Proteins; D009566:Nitrates; D017680:Potassium Compounds; D027961:Potassium-Hydrogen Antiporters; D004024:Dicyclohexylcarbodiimide; D011803:Quinine; D011796:Quinacrine; D008274:Magnesium; D019342:Acetic Acid; D009550:Nigericin; C023844:potassium nitrate