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 (NH(4)(+)) transport along the collecting duct has been thought to occur through active H(+) section in parallel with the nonionic diffusion of ammonia (NH(3)). This model is supported by two basic experimental observations. First, NH(4)(+) secretion generally correlates with the NH(3) concentration gradient between the interstitium and the collecting duct lumen. This NH(3) gradient is generated through both luminal acidification, which reduces luminal NH(3) concentration, and through countercurrent multiplication, which increases interstitial NH(3) concentration. The result is secretion of NH(3) into the collecting duct lumen down its concentration gradient. Second, because NH(4)(+) permeability is low relative to that of NH(3), there is significant secretion of NH(3) into the collecting duct lumen with minimal back-diffusion of NH(4)(+). However, our laboratory, as well as others, has shown that this model is an oversimplification of the mechanism of NH(4)(+) transport along the collecting duct. NH(4)(+) is transported through a variety of K(+) transport pathways including Na,K-ATPase. K(+) and NH(4)(+) compete for a common extracellular binding site on Na, K-ATPase. During hypokalemia, interstitial K(+) concentration is reduced, which augments NH(4)(+) uptake by the Na(+) pump. In K(+) restriction, Na,K-ATPase-mediated NH(4)(+) uptake provides an important source of H(+) for net acid secretion and for the titration of luminal buffers in the terminal inner medullary collecting duct. This pathway contributes to the increase in NH(4)(+) excretion and metabolic alkalosis observed during hypokalemia.