Computational studies of ion-water flux coupling in the airway epithelium. I. Construction of model

A mathematical model of ion and water transport across the airway epithelium is presented. The model consists of 12 state variables representing ion concentrations, volumes, and membrane potentials. All osmotically significant membrane transport processes for which there is conclusive experimental evidence are included: passive apical sodium and chloride movement, basolateral sodium-potassium pumping, basolateral sodium- potassium-chloride cotransport, passive basolateral potassium movement, nonselective passive paracellular ion motion, and water transport across all membranes. Ion movements are described by Michaelis-Menten kinetics or by the constant field flux equation. Model parameters are established with Ussing chamber data. Model behavior is validated by comparing in vitro simulations with experimental results. The model accurately reproduces short-circuit chloride and sodium fluxes, short-circuit current, and open-circuit membrane potentials from Ussing chamber data in the secreting and nonsecreting states. The model is then used to describe the behavior of the airway epithelium in vivo, in which case the apical electrolyte compartment is small and of variable size and ionic composition.