Impact of K+ homeostasis on net acid secretion in rat terminal inner medullary collecting duct: Role of the Na,K-ATPase

For the past 50 years, the mechanism of ammonium (NH4+) transport along the collecting duct has been thought to occur through active H+ secetion in pa rallel with the nonionic diffusion of ammonia (NH3), This model is supporte d by two basic experimental observations. First, NH4+ secretion generally c orrelates with the NH3 concentration gradient between the interstitium and the collecting duct lumen. This NH3 gradient is generated through both lumi nal acidification, which reduces luminal NH3 concentration, and through cou ntercurrent multiplication, which increases interstitial NH3 concentration, The result is secretion of NH3 into the collecting duct lumen down its con centration gradient, Second, because NH4+ permeability is low relative to t hat of NH3, there is significant secretion of NH3 into the collecting duct lumen with minimal back-diffusion of NH4+. However, our laboratory, as well as others, has shown that this model is an oversimplification of the mecha nism of NH4+ transport along the collecting duct. NH4+ is transported throu gh a variety of K+ transport pathways including Na,K-ATPase, K+ and NH4+ co mpete for a common extracellular binding site on Na,K-ATPase, During hypoka lemia, interstitial K+ concentration is reduced, which augments NH4+ uptake by the Nai pump. In K+ restriction, Na,K-ATPase-mediated NH4+ uptake provi des an important source of H+ for net acid secretion and for the titration of luminal buffers in the terminal inner medullary collecting duct. This pa thway contributes to the increase in NH4+ excretion and metabolic alkalosis observed during hypokalemia, (C) 2000 by the National Kidney Foundation, I nc.