Weak acids, weak bases and intracellular pH

Against the background of classical observations made 50 years ago, a brief review is offered of some of the work performed in the author's laboratory on the behavior of weak acids and bases towards living animal cells. The significance of membrane permeability of the charged partner of these electrolytes is pointed out, and the existence of an active process of H+ extrusion (or its equivalent) in response to acid loading is demonstrated. The effect of intracellular inhomogeneity on weak acid and base transmembrane distribution is examined. The significance of these variables for weak acid- or base-derived intracellular pH is discussed.