Effects of medium acetate on cellular volume in rabbit renal cortical slices

Slices of rabbit renal cortex were incubated at 25 degrees C in media in which acetate replaced chloride. There was gross cellular swelling in isosmotic 132 mM-acetate medium, and this swelling was unique in that, with a normal medium potassium concentration, it was accompanied by a substantial increase in cellular potassium content. This accumulation of potassium, but not the cellular swelling, was dependent upon metabolism and inhibited by ouabain. This accumulation of potassium was not dependent upon the cellular swelling. It also occurred in a hyperosmotic acetate medium in which swelling was minimized. In isosmotic media, the cellular swelling was proportional to medium acetate concentration and was also affected markedly by medium pH, being greatest at an initial medium pH of 7.1 and least at pH 7.7. The swelling was reversed and cellular composition restored when tissue was re-incubated in NaCl medium. Ouabain (10(-3)M) largely prevented this recovery in volume. The results are consistent with plasma-membrane-based theories, on the assumption that membranes are much more permeable to undissociated acetic acid than they are to the acetate ion. They are inconsistent with the expectations of an alternative hypothesis (the association--induction hypothesis) which ascribes the maintenance of cellular composition to properties of cellular proteins and cellular water rather than to those of the plasma membrane. The results do not favour the suggestion that cellular swelling itself results in irreversible cellular damage. The results are consistent with the hypothesis that the ouabain-inhibitable Na-K-ATPase plays a major role in the regulation of cellular volume. No alternative metabolically dependent volume regulating mechanism need be postulated to explain them.