Cytoplasmic pH determines K+ conductance in fused renal epithelial cells

The mineralocorticoid hormone aldosterone maintains acid-base balance and K+ homeostasis by regulating H+ and K+ secretory mechanisms in kidney epithelial cells. We have shown recently in the amphibian distal nephron that aldosterone activates a Na+/H+ exchange system in the luminal cell membrane, thus leading to transepithelial H+ secretion and cytoplasmic alkalinization. Since H+ secretory fluxes were paralleled by K+ secretion, it was postulated that the hormone-induced increase of intracellular pH activates the luminally located K+ channels. In "giant" cells fused from individual cells of the distal nephron, we measured simultaneously cytoplasmic pH and cell membrane K+ conductance during acidification of the cell cytoplasm. The experiments show that cell membrane K+ conductance is half-maximal at an intracellular pH of 7.42 and that a positive cooperative interaction exists between K+-channel proteins and H+ (Hill coefficient = 6.5). Moreover, the cellular K+ conductance is most sensitive to cytoplasmic pH in the range modified by aldosterone. This supports the hypothesis that intracellular H+ activity, regulated by the Na+/H+ exchanger, serves as the signal to couple aldosterone-induced K+ secretory flux to H+ secretion in renal tubules.