N,N'-Dicyclohexylcarbodiimide inhibits monovalent cation influx but not cation/proton exchange in heart mitochondria.

N,W-Dicyclohexylcarbodiimide (DCCD) inhibits the net, respiration-dependent uptake of monovalent cations by isolated heart mitochondria which occurs spontaneously in acetate and phosphate salts and in chloride salts following addition of trialkyltins.The accumulation of ions is less efficient in the presence of DCCD, although identical membrane potentials as reported by safranine distribution are maintained in DCCD-treated and control mitochondria.Net uptake of K+ and osmotic swelling in the presence of valinomycin are not inhibited by DCCD.These results suggest that DCCD restricts the electrophoretic influx of cations via the uniport (or leak) pathwayswhich are normally open under these conditions.2. In contrast to these effects on respiration-dependent ion uptake, the passive influx of Na' which occurs spontaneously in acetate and phosphate and is induced by trialkyltin in Na' chloride is not affected by DCCD.Net ion influx under these conditions has been attributed to an endogenous Na'/H' exchange component.3. DCCD inhibits the passive influx of K' and Na' and osmotic swelling which occurs at elevated pH when heart mitochondria are suspended in nitrate salts.However, DCCD strongly enhances the rate, extent, and efficiency of respiration-dependent ion extrusion and osmotic contraction of mitochondria swollen at pH 8.3 in nitrate salts.The ability of this inhibitor to block passive ion influx but to stimulate respiration-dependent contraction provides strong evidence that influx and efflux of ions occur by different pathways.4. The effects of DCCD on cation influx appear to be distinct from the well established interaction of this reagent with a membrane proteolipid in the protontranslocating ATPase.