Model of ion transport regulation in chloride-secreting airway epithelial cells. Integrated description of electrical, chemical, and fluorescence measurements

Abstract

An electrokinetic model was developed to calculate the time course of electrical parameters, ion fluxes, and intracellular ion activities for experiments performed in airway epithelial cells. Model variables included cell [Na], [K], [Cl], volume, and membrane potentials. The model contained apical membrane Cl, Na, and K conductances, basolateral membrane K conductance, Na/K/2 Cl and Na/Cl symport, and 3 Na/2 K ATPase, and a paracellular conductance. Transporter permeabilities and ion saturabilities were determined from reported ion flux data and membrane potentials in intact canine trachea. Without additional assumptions, the model predicted accurately the measured short-circuit current (Isc), cellular conductances, voltage-divider ratios, open-circuit potentials, and the time course of cell ion composition in ion substitution experiments. The model was used to examine quantitatively: (a) the effect of transport inhibitors on Isc and membrane potentials, (b) the dual role of apical Cl and basolateral K conductance in cell secretion, (c) whether the basolateral symporter requires K, and (d) the regulation of apical Cl conductance by cAMP and Ca-dependent signaling pathways. Model predictions gave improved understanding of the interrelations among transporting systems and in many cases gave surprising predictions that were not obvious without a detailed model. The model developed here has direct application to secretory or absorptive epithelial cells in the kidney thick ascending limb, cornea, sweat duct, and intestine in normal and pathophysiological states such as cystic fibrosis and cholera.

Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells

“…2-4), and bafilomycin-induced alkalinization data were obtained from the literature (Table 2). These P H ϩ values are large compared with typical permeability values for Na ϩ , K ϩ , and Cl Ϫ : 10 Ϫ12 cm/s for a membrane without channels (37) and up to 10 Ϫ5 cm/s for a membrane with channels (22,24). However, our estimates of P H ϩ compare favorably with P H ϩ in lipid bilayers and liposomes: 10 Ϫ7 -10 Ϫ2 cm/s (8,21,37,40).…”

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

“…7 and 8 we integrate the net flow of each species over the length of the time step to update the concentrations. This iterative calculation of the membrane potentials is well proven for epithelial models (25,43,85). A detailed description of our implementation and validation of the iterative method is given in Iterative Calculation of Membrane Potentials.…”

Mechanisms of pH Regulation in the Regulated Secretory Pathway

“…Therefore, in predicting P Hϩ we assumed that both K ϩ and Cl Ϫ were free to diffuse across the organelle membranes. We chose permeability coefficients for these ions of ϳ10 Ϫ5 cm/s based upon plasma membrane measurements (35). Our numeric results remain unaffected for counterion permeability values down to 10 Ϫ9 cm/s.…”