Ion Transport by Heart Mitochondria

Abstract The energy-linked accumulation of Mg++ by isolated heart mitochondria has been studied with the use of exogenous adenosine triphosphate as the source of energy. In common with the substrate-supported accumulation of Mg++, the ATP-supported reaction is activated by the addition of Zn++, Cd++, and certain other heavy metal cations under the appropriate conditions. In sharp contrast with the substrate reaction, however, it was found that the ATP-supported reaction is also strongly activated by p-chloromercuriphenylsulfonate (CMS). The combination of Zn++ and CMS strongly inhibits the substrate-dependent accumulation of Mg++, but produces a remarkable enhancement of Mg++ uptake in the presence of ATP. The increased accumulation of Mg++ and the increased ATPase activity which accompanied the accumulation are both inhibited by oligomycin. The accumulation of Mg++ by this pathway is much less sensitive to low levels of dinitrophenol than is the substrate-dependent reaction. When both substrate and ATP are available as energy sources for Mg++ accumulation, and the reaction is activated by Zn++, the uptake of Mg++ is sensitive to dinitrophenol and insensitive to oligomycin. Addition of CMS under these conditions reverses this pattern of inhibition so that the accumulation becomes sensitive to oligomycin but insensitive to dinitrophenol. The available evidence indicates that Zn++ may act directly on the process responsible for the uptake of Mg++, perhaps by altering the permeability of the membrane. The mercurial (CMS), however, appears to have its primary effect on the energy transfer process. Evidence is presented that this reagent blocks energy transfer between the dinitrophenol-sensitive site and the site which energizes the Mg++ uptake process. In addition, CMS may activate mitochondrial ATPase in such a way that more energy is available for the accumulation of Mg++.