Fig. 6.

Model of collecting duct ammonia secretion. In the interstitium, NH₄⁺ is in equilibrium with NH₃ and H⁺. NH₃ is transported across the basolateral membrane through both Rhesus glycoproteins Rhbg and Rhcg. In the IMCD, basolateral Na⁺-K⁺-ATPase is a major mechanism of basolateral NH₄⁺ uptake, followed by dissociation of NH₄⁺ to NH₃ and H⁺ (grey lines). Intracellular NH₃ is secreted across the apical membrane by apical Rhcg. H⁺ secreted by H⁺-ATPase and H⁺-K⁺-ATPase combine with luminal NH₃ to form NH₄⁺, which is “trapped” in the lumen. In addition, there may also be minor components of diffusive NH₃ movement across both the basolateral and apical plasma membranes (dotted lines). The intracellular H⁺ that is secreted by H⁺-ATPase and H⁺-K⁺-ATPase is generated by carbonic anhydrase (CA) II-accelerated CO₂ hydration that forms carbonic acid, which dissociates to H⁺ and HCO₃⁻. Basolateral Cl⁻/HCO₃⁻ exchange transports HCO₃⁻ across the basolateral membrane; HCO₃⁻ combines with H⁺ released from NH₄⁺, to form carbonic acid, which dissociates to CO₂ and water. This CO₂ can recycle into the cell, supplying the CO₂ used for cytosolic H⁺ production. The net result is NH₄⁺ transport from the peritubular space into the luminal fluid. In the non-A, non-B cell, which lacks substantial basolateral Rhcg expression, Rhbg is likely the primary basolateral NH₃ transport mechanism. The B-type intercalated cell, which lacks detectable Rhbg and Rhcg expression, likely mediates transcellular ammonia secretion through mechanisms only involving lipid-phase NH₃ diffusion and thus transports ammonia at significantly slower rates.