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/sup +/-ATPase (V-ATPase), Na/sup +//H/sup +/ exchanger, and Na/sup +/-independent HCO/sub 3//sup -/ /Cl/sup /exchanger. Since V-ATPase-mediated H/sup +/ extrusion is electrogenic, alterations in membrane potential (and cell volume) occur during experimental acid-loading and subsequent pH/sub 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/sup +/, K/sup +/, and Cl/sup -/, and associated ion currents through ion channels. The model was used to analyze the acid-base responses of rabbit alveolar m/spl phi/ to an NH/sub 3/ prepulse acid-load. Our results indicate that there are substantial problems with quantifying transporter-mediated H/sup +/ efflux solely from experimental observations of pH/sub i/ recovery due to residual NH/sub 4//sup +/ efflux from the macrophage.