title: Biophysical model of ion transport across human respiratory epithelia allows quantification of ion permeabilities.
abstract: Lung health and normal mucus clearance depend on adequate hydration of airway surfaces. Because transepithelial osmotic gradients drive water flows, sufficient hydration of the airway surface liquid depends on a balance between ion secretion and absorption by respiratory epithelia. In vitro experiments using cultures of primary human nasal epithelia and human bronchial epithelia have established many of the biophysical processes involved in airway surface liquid homeostasis. Most experimental studies, however, have focused on the apical membrane, despite the fact that ion transport across respiratory epithelia involves both cellular and paracellular pathways. In fact, the ion permeabilities of the basolateral membrane and paracellular pathway remain largely unknown. Here we use a biophysical model for water and ion transport to quantify ion permeabilities of all pathways (apical, basolateral, paracellular) in human nasal epithelia cultures using experimental (Ussing Chamber and microelectrode) data reported in the literature. We derive analytical formulas for the steady-state short-circuit current and membrane potential, which are for polarized epithelia the equivalent of the Goldman-Hodgkin-Katz equation for single isolated cells. These relations allow parameter estimation to be performed efficiently. By providing a method to quantify all the ion permeabilities of respiratory epithelia, the model may aid us in understanding the physiology that regulates normal airway surface hydration.
authors: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. guihermejmgarcia@gmail.com
authors: Guilherme J M
authors: GJ
authors: Garcia
authors: Richard C
authors: RC
authors: Boucher
authors: Timothy C
authors: TC
authors: Elston
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D007700:Kinetics; D008564:Membrane Potentials; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D015221:Potassium Channels; C578877:SLC12A2 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium