The effect of oligomycin on net movements of sodium and potassium in mammalian cells in vitro

Abstract

1. 1. The effects of oligomycin on the net accumulation of potassium and net loss of sodium by whole mammalian cells have been studied. Three types of cell system, differing in the relationship of the cation movements to the energy-providing metabolism, were used. 2. 2. In liver slices prepared from adult rats oligomycin inhibited sodium and potassium movements by a maximum of 50%. Half-maximal inhibition of potassium uptake was given by oligomycin at a concentration of approx. 3 μg/ml (0.29 μg/mg liver-slice protein). The 50% of the potassium uptake which persisted in the presence of oligomycin was largely inhibited by the further addition of cyanide or 2,4-dinitrophenol. 3. 3. Oligomycin inhibited respiration of the adult tissue by a maximum of 20%, half-maximal inhibition being given by 3 μg/ml oligomycin (0.29 μg/mg protein). The inhibition was released by the further addition of dinitrophenol. 4. 4. Slices of liver prepared from rat foetuses during the last 2 days of gestation can accumulate a considerable amount of potassium when incubated in the presence of cyanide. Oligomycin gave approx. 50% inhibition of this cyanide-resistant accumulation of potassium, the half-maximal effect being given by an oligomycin concentration of about 3 μg/ml (0.41 μg/mg liver-slice protein). In the absence of oligomycin, dinitrophenol almost completely inhibited cyanide-resistant potassium accumulation. In the presence of oligomycin, part of the potassium accumulation remained uninhibited by dinitrophenol. 5. 5. Oligomycin did not inhibit anaerobic glycolysis in the slices of foetal liver. 6. 6. Oligomycin, at concentrations of 10 and 20 μg/ml, had no effect upon net sodium movements in human erythrocytes. In contrast, strophanthin G inhibited the sodium movements. 7. 7. Consideration of these results in relation to the known effects of oligomycin on enzyme activities in subcellular particles suggests that oligomycin probably inhibited cation movements in liver slices by virtue of its inhibitory effect upon oxidative phosphorylation, rather than by inhibition of a reaction directly involved in cation transport. If this conclusion is correct, it follows that part of the energy required for cation transport by liver cells can be derived directly from an energy-rich intermediate of oxidative phosphorylation.