Ion transport in lung cells: from cellular homeostasis to pulmonary gas exchange

Alveolar epithelial cells (types I and II), red blood cells (RBC), alveolar macrophages (mφ), and the pulmonary capillary endothelium share transport and chemical reaction processes that are vital for whole lung O₂ uptake and CO₂ excretion, as well as, cellular ion homeostasis. We have developed detailed mathematical models for each of these component units, incorporating molecular events that are intrinsic to their homeostatic function. The models were used in conjunction with tightly-coupled experimental studies of isolated cells and whole lung to gain insight into: (a) the role of RBC anion exchange and carbonic anhydrase (CA)-catalyzed CO₂-HCO₃^- reactions in CO₂ excretion and intravascular pH equilibration; (b) regulation of cell pH; and (c) regulation of cell volume and major cytosolic osmolyte (Na⁺, K⁺, and Cl^-) concentrations. These coupled theoretical-experimental studies provide important insights into kinetic properties of the ion transporters, and the extent and role of CA activity in the lung.