Aldosterone-controlled linkage between Na+/H+ exchange and K+ channels in fused renal epithelial cells

Aldosterone maintains acid-base balance and K+ homeostasis by controlling H+ and K+ secretion in renal epithelial cells. We have shown recently in the amphibian distal nephron that aldosterone activates a Na+/H+ exchange system in the luminal cell membrane, leading to transepithelial H+ secretion and cytoplasmic alkalinization. Since H+ secretory fluxes are 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 demonstrate 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+ ions (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.