Airway surface liquid volume expansion induces rapid changes in amiloride-sensitive Na+ transport across upper airway epithelium-Implications concerning the resolution of pulmonary edema

Fouad Azizi, Abdelilah Arredouani, Ramzi M. Mohammad

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Abstract

During airway inflammation, airway surface liquid volume (ASLV) expansion may result from the movement of plasma proteins and excess liquid into the airway lumen due to extravasation and elevation of subepithelial hydrostatic pressure. We previously demonstrated that elevation of submucosal hydrostatic pressure increases airway epithelium permeability resulting in ASLV expansion by 500 µL cm-2 h-1. Liquid reabsorption by healthy airway epithelium is regulated by active Na+ transport at a rate of 5 µL cm-2 h-1. Thus, during inflammation the airway epithelium may be submerged by a large volume of luminal liquid. Here, we have investigated the mechanism by which ASLV expansion alters active epithelial Na+ transport, and we have characterized the time course of the change. We used primary cultures of tracheal airway epithelium maintained under air interface (basal ASLV, depth is 7 ± 0.5 µm). To mimic airway flooding, ASLV was expanded to a depth of 5 mm. On switching from basal to expanded ASLV conditions, short-circuit current (Isc, a measure of total transepithelial active ion transport) declined by 90% with a half-time (t1/2) of 1 h. 24 h after the switch, there was no significant change in ATP concentration nor in the number of functional sodium pumps as revealed by [3H]-ouabain binding. However, amiloride-sensitive uptake of 22Na+ was reduced by 70% upon ASLV expansion. This process is reversible since after returning cells back to air interface, Isc recovered with a t1/2 of 5-10 h. These results may have important clinical implications concerning the development of Na+ channels activators and resolution of pulmonary edema.

Original languageEnglish
Article numbere12453
JournalPhysiological Reports
Volume3
Issue number9
DOIs
Publication statusPublished - 2015

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Keywords

  • Airway epithelium
  • Airway surface liquid
  • Edema
  • Na transport
  • Sodium pumps

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

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