Induction of respiration-dependent net efflux of K+ from heart mitochondria by depletion of endogenous divalent cations.

1. Ionophore A23187 depletes the endogenous Mg2+ of beef heart mitochondria to 4 ng ions . mg-1 (or less) and Ca2+ to less than 2 ng ions . mg-1 in a reaction which does not require metabolic energy. Ionophore A23187 also promotes the near quantitative extrusion of endogenous K+ from heart mitochondria to a K+-free medium, but this reaction requires respiration and is sensitive to uncouplers. Respiring mitochondria which extrude K+ in the presence of A23187 maintain high membrane potentials and do not swell. The K+ depletion has the properties of a K+/H+ exchange reaction occurring at the expense of delta pH of respiration. 2. The rate and extent of K+ efflux are dependent on the removal of endogenous divalent cations by A23187, but are otherwise independent of the amount of A23187 present. It is concluded that K+ efflux results from activation of an endogenous K+/H+ exchange component and that A23187 does not function directly as a K+/H+ exchanger in mitochondria.