PROTON PERMEABILITY AND REGULATION OF POTASSIUM PERMEABILITY IN MITOCHONDRIA BY UNCOUPLING AGENTS

The addition of agents that uncouple electron transfer from energy conservation (uncouplers) to state 4 mitochondria causes the following ion movements: K+ is extruded from the mitochondria in association with phosphate and possibly other anions, but not H+. Endogenous Ca++ is extruded from the mitochondria, and H+ moves in to counter-balance the Ca++ movement; some phosphate movement may be associated with Ca++ extrusion. The rate and extent of K+ extrusion induced by uncoupler is dependent on the concentrations of external phosphate and divalent ions. Phosphate induces K+ extrusion, while Mg++ and Mn++ inhibit it. The Vmax of K+ transport is 300 μmoles K+/g protein per min. The Km for FCCP-induced potassium extrusion is 0.25 μM at pH 7.4. The inhibitory effect of Mg++ is noncompetitive with respect to uncoupler concentration but competitive with respect to phosphate concentration. The experimental evidence does not support the existence of high H+ permeability in the presence of uncoupler. A correlation is observed between the rate of K+ extrusion and the energy reserves supplied from the high energy intermediate. The action of uncoupler in inducing K+ permeability is considered to arise through its action in depleting the energy reserves of mitochondria rather than through a specific activating effect of permeability by the uncoupler itself. The relationship of membrane potential to regulation of K+ permeability is discussed. © 1969 Springer-Verlag New York Inc.