NH4+ transport in the kidney.

We have described the overall process that is responsible for the efficient transfer of ammonium from its production site in the proximal tubule cells to the final urine. The mechanism depends on direct NH4+ transport at a number of sites. There appears to be a predominance of NH3 over NH4+ transport in net total ammonia transport only in the collecting ducts and possibly the descending limbs of Henle's loop. Several examples of physiologically important direct NH4+ transport in the kidney were described. First, coupled Na/NH4/2Cl transport across the apical membrane of the thick ascending limb of Henle's loop mediates secondary active transport of ammonium, which drives countercurrent multiplication of ammonium in the renal medulla. Second, part of the NH4+ uptake across the apical membrane of the thick ascending limb may occur as a result of penetration by NH4+ through apical K+ channels. It is unknown whether NH4+ penetrates K+ channels in other tubule segments. Third, NH4+ can be actively transported into cells by substitution of NH4+ for K+ on the Na-K-ATPase. This NH4+ transport process is likely to be rapid enough to be physiologically significant only in the inner medulla, where NH4+ concentrations are high enough to successfully compete with K+. Fourth, NH4+ penetrates the paracellular pathway in some nephron segments such as the proximal tubule and thick ascending limb. Simple passive diffusion of NH4+ via the paracellular pathway is thought to be physiologically important in the thick ascending limb where it contributes to net NH4+ absorption.