A mathematical model of the airway epithelium: Computational studies of ion and water balance
Novotny-Dura, Janet Anne
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Permalink
https://hdl.handle.net/2142/23405
Description
Title
A mathematical model of the airway epithelium: Computational studies of ion and water balance
Author(s)
Novotny-Dura, Janet Anne
Issue Date
1993
Doctoral Committee Chair(s)
Jakobsson, Eric
Department of Study
Biophysics
Discipline
Biophysics
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Animal Physiology
Biophysics, General
Language
eng
Abstract
A mathematical model has been developed to investigate the time course of ion and water transport across airway epithelia. Model variables were intracellular and apical concentrations of sodium, potassium, chloride; apical, basolateral, and transepithelial membrane potentials; cell and apical volumes. Membrane transport processes included apical passive diffusion of sodium and chloride, basolateral passive diffusion of potassium, basolateral sodium-potassium active transport, basolateral sodium-potassium-chloride cotransport, water permeation across all membranes, and nonselective paracellular passive diffusion of sodium, potassium, and chloride. Initial conditions and transport parameters were derived from experimental results.
To test the model, simulations were performed for epithelia in an Ussing chamber. The model predicted short-circuit currents, short-circuit ion fluxes, intracellular ion concentrations, and open circuit voltages consistent with experimental data.
The model was used to investigate the behavior of airway epithelia in vivo. Simulations of the cystic fibrosis defect showed that decreased apical chloride permeability and increased apical sodium permeability both decrease water flow from the basal side toward the airway lumen. We also show that blockage of apical sodium channels could compensate completely for airway dehydration due to defective apical chloride channels of cystic fibrosis airway epithelia.
Other simulations determined the role of the various ion transport mechanisms observed in this tissue. The basolateral potassium permeability maintains the apical membrane voltage and allows potassium to exit the cell. The basolateral sodium-potassium pump is necessary to maintain sodium and potassium gradients. The basolateral sodium-potassium-chloride cotransporter is essential for salt movement from the basal region to the cytoplasm to promote water flux across the basolateral membrane. The apical chloride channels allow chloride efflux, drawing water into the apical region to replace that lost by evaporation. The apical sodium channels allow sodium absorption from the apical side to the basal side of the tissue. The paracellular path permits movement of chloride, to recycle chloride which is secreted across the apical membrane, and movement of sodium, to replace sodium which is absorbed across the apical membrane. Finally, water permeation across cell membranes is vital for replacement of water lost from the periciliary fluid by evaporation.
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