COMPUTATIONAL STUDIES OF ION-WATER FLUX COUPLING IN THE AIRWAY EPITHELIUM .2. ROLE OF SPECIFIC TRANSPORT MECHANISMS

Ion and water balance by the in vivo airway epithelium was investigate d utilizing dynamic computer modeling. Parameters of the osmotically s ignificant transport processes were varied to assess the sensitivity o f water transport and fluid composition to transport perturbations. Es tablishment and regulation of water secretion represent a coordinated function of at least seven different ion transport processes: basolate ral passive potassium transport, basolateral active sodium-potassium t ransport, basolateral sodium-potassium-chloride cotransport, apical pa ssive sodium and chloride transport, and diffusion of sodium and chlor ide across the paracellular path. We found that apical chloride permea bility at-a level reported for cystic fibrosis is sufficient to cause the airway dehydration characteristic of cystic fibrosis. Given the re duction in apical chloride permeability in cystic fibrosis, a reductio n in apical sodium permeability can potentially compensate completely for the airway dehydration associated with the cystic fibrosis genetic defect; Other simulations presented here address the importance of va rious membrane transport processes in airway epithelium water balance and the sensitivity of epithelium water balance to ion transport pertu rbations.