Potassium-specific Uncoupling by Nigericin*

The uncoupling activity of nigericin in rat liver mitochondria was found to be proportional to the external concentration of potassium. Rubidium (40% as effective as potassium) was the only other alkali metal cation that permitted significant uncoupling. The ability of nigericin selectively to inhibit (at low concentrations) and to uncouple (at high concentrations) only certain substrates was investigated with particular reference to glutamate and malate. The rate-limiting reaction for glutamate oxidation in the presence of nigericin was substrate level phosphorylation, not glutamate uptake. Nigericin was compared with other uncouplers with respect to induced ion movements and relative effectiveness in overcoming respiratory inhibition by guanidine compounds. Nigericin potentiated rather than reversed the guanidine inhibition. Possible mechanisms for the involvement of the potassium complex of nigericin in the uncoupling process are discussed.