Mechanisms of NH4+ and NH3 transport during hypokalemia

Along the collecting duct, secretion of ammonium (NH) is thought to occur through active H+ secretion in parallel with the non-ionic diffusion of ammonia (NH3). Thus NH3 is secreted into the collecting duct lumen down its concentration gradient. Moreover, the low NH permeability and high NH3 permeability observed in collecting duct epithelia minimizes back diffusion of NH. In general, an increase in the NH3 concentration gradient between the interstitium and the collecting duct lumen correlates with increased NH secretion. However, our laboratory and others have shown an important role of direct NH transport by the Na,K-ATPase. As K+ and NH compete for a common extracellular binding site on the Na,K-ATPase, reduced interstitial K+ concentration, such as during hypokalemia, augments NH uptake. Na,K-ATPase-mediated NH uptake provides an important source of H+ for net acid secretion during hypokalemia and contributes to the increase in NH excretion and metabolic alkalosis observed in this treatment model.