Title: Modeling Airway Epithelial Ion Transport in Ussing Chambers
Abstract: Airway epithelial ion transport regulates airway-surface fluid and is strongly altered in cystic fibrosis. We develop a mathematical model for epithelial sodium, potassium, and chloride transport motivated by Ussing-chamber experiments. The model couples nonlinear membrane flux laws, pump and cotransporter kinetics, paracellular transport, and osmotic cell-volume dynamics. Exploiting the separation between fast volume equilibration and slower ionic dynamics, we derive a reduced system with algebraic constraints and analyze the resulting differential-algebraic equations under short-circuit and open-circuit conditions. We then study parameter sensitivity and pharmacological perturbations to identify how individual transport pathways influence measured current and voltage. Comparison with experimental nasal potential-difference data reveals that reducing apical chloride permeability alone does not reproduce the cystic-fibrosis voltage phenotype, suggesting that additional transport mechanisms may be required.