Effect of metabolic inhibitors on renal tubule cell volume

Renal tubule cell volume is thought to be kept constant by a cation pump. Ouabain, by inhibiting Na+-K+-ATPase, blocks cation transport with resultant cell swelling, but the degree of swelling is less than expected were active cation transport completely inhibited. Although the relatively rigid tubule basement membrane may limit swelling of ouabain-treated tubules, some investigators have alternatively postulated that an energy-dependent ouabain-insensitive cation pump regulates cell size. This notion derives from studies of renal cortical slices in which metabolic inhibitors such as 2,4-dinitrophenol (DNP) cause more swelling than ouabain. We blocked cellular metabolism of isolated rabbit proximal straight tubules by adding metabolic inhibitors to or removing acetate and glucose (energy substrate) from the bathing medium and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. In isotonic medium, cell volume increased 36% with addition of 10(-4) M ouabain, 40% with 10(-2) M DNP, 46% with 10(-3) M cyanide, 39% with ouabain + DNP + cyanide, and 37% with removal of bath substrate (P = NS). We conclude that renal tubule cell volume is not regulated by a unique-ouabain-insensitive cation pump.