Regulation of Airway Surface Liquid Volume in Cystic Fibrosis Epithelia

Hydration of the airway surface liquid (ASL) that covers the respiratory tract is regulated by a complex signaling network. The Airway Biomechanics Laboratory is developing a mathematical model of ASL volume and pH regulation. Applications of this mathematical model include the interpretation of electrophysiology experiments and the development of pharmaceutical drugs to treat cystic fibrosis (CF). For example, the mathematical model can be used to quantify how ion channel blockers affect intracellular and extracellular ion concentrations, membrane potentials, ASL volume, and ASL pH.

Model illustrating ion transport between the apical, cellular and basolateral compartments.

Figure 1:  Diagram of ion transport pathways included in our first mathematical model of airway epithelia electrophysiology (Garcia et al, 2013, Biophysical Journal 104, 716-726). 

Figure illustrating ion transport between epithelial cell and airway surface liquid.

Figure 2:  Signaling pathways regulating airway surface liquid volume included in our current mathematical model. 

 

Selected Publications

Amarante T.D., da Silva J.K.L., Garcia G.J.M. (2014) Effects of airway surface liquid height on the kinetics of extracellular nucleotides in airway epithelia. Journal of Theoretical Biology 363, 427-435.

Kota P., Buchner G., Chakraborty H., Dang YL., He H., Garcia G.J.M., Kubelka J., Gentzsch M., Stutts M.J., Dokholyan N.V. (2014) The N-terminal Domain Allosterically Regulates Cleavage and Activation of the Epithelial Sodium Channel. Journal of Biological Chemistry 289, 23029-23042.

Garcia G.J.M., Boucher R.C., Elston T.C. (2013) Biophysical model of ion transport across human respiratory epithelia allows quantification of ion permeabilities. Biophysical Journal 104, 716-726.

Garcia G.J.M., Picher M., Zuo P., Okada S.F., Lazarowski E.R., Button B., Boucher R.C., Elston T.C. (2011) Computational model for the regulation of extracellular ATP and adenosine in airway epithelia. In Purinergic regulation of respiratory diseases (M. Picher and R.C. Boucher, eds.), Chapter 3, Springer Publishing, ISBN-13: 978-9400712164. Subcell Biochem. 55, 51-74.

 

 

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