Mathematical analysis of alveolar macrophage pH regulation

Alveolar macrophage cell pH is maintained by the complex interactions of three acid-base transporters: plasmalemma vacuolar-type H⁺-ATPase (V-ATPase), Na⁺/H⁺ exchanger, and Na⁺-independent HCO₃^- /Cl^$exchanger. Since V-ATPase-mediated H⁺ extrusion is electrogenic, alterations in membrane potential (and cell volume) occur during experimental acid-loading and subsequent pH_i recovery. We have developed a nonlinear mathematical model that incorporates the biophysical determinants of cell pH, cell volume, the transmembrane fluxes of individual acid-base equivalents, fluxes of Na⁺, K⁺, and Cl^-, and associated ion currents through ion channels. The model was used to analyze the acid-base responses of rabbit alveolar mφ to an NH₃ prepulse acid-load. Our results indicate that there are substantial problems with quantifying transporter-mediated H⁺ efflux solely from experimental observations of pH_i recovery due to residual NH₄⁺ efflux from the macrophage.