Fig. 4. Airway epithelial H⁺ and HCO₃^- transport determines ASL pH.

A. Distribution of H⁺ and HCO₃^- transporters in lung epithelium. The HVCN1 H⁺ conductance and the CFTR HCO₃^- conductance are expressed apically. HVCN1 conducts H⁺ only outwardly while CFTR conducts HCO₃^- both ways. The Na⁺-H⁺ exchanger NHE1, the Cl^--HCO₃^- anion exchanger AE2, and the Na⁺-HCO₃^- cotransporter NBC1 are present in the basolateral membrane. Resting pH values for the airway surface liquid (pH_ASL), intracellularly (pH_i), and serosally (pH_ser) are given. For stoichiometry of transporters see (28, 78). B. ASL pH determines airway H⁺ and HCO₃^- secretion. HCO₃^- secretion (open symbols) is modeled for pH_i 6.95; V_a -24 mV; apical, linear, voltage-independent HCO₃^- conductance 0.4 mS/cm²; average pCO₂ 3 kPa. H⁺ secretion data (filled symbols) are mean±SE compiled from previous measurements (17, 19). C. Predicted change of ASL pH by H⁺ and HCO₃^- secretion. Calculated from rates in B using buffer capacities for the ASL from ref. (65) (range 6.5 to 15 mM/pH) and an ASL volume of 1.5 μl/cm². CFTR, cystic fibrosis transmembrane conductance regulator.