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Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice
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Functional Differences in Electrolyte Transport Between the Mouse Proximal and Distal Trachea.

Tábata Apablaza1,2, Sandra Villanueva1,3, Araceli Olave-Ruiz1,4

  • 1Centro de Estudios Científicos (CECs), Valdivia, Chile.

Acta Physiologica (Oxford, England)
|June 26, 2026
PubMed
Summary
This summary is machine-generated.

The mouse trachea has distinct proximal and distal regions with specialized functions in fluid transport. The distal trachea, unlike the proximal, responds to inflammation by altering ion transport.

Keywords:
ASCL3NBCe1NKCC1TMEM16AUssing chambertrachea

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Area of Science:

  • Physiology
  • Molecular Biology
  • Respiratory Medicine

Background:

  • The mammalian tracheal epithelium exhibits regional specialization along the proximal-distal axis.
  • Variations in ion channel and transporter function for fluid absorption/secretion between proximal and distal mouse trachea remain understudied.

Purpose of the Study:

  • To characterize and compare basal and stimulated fluid absorption and secretion in proximal and distal mouse trachea.
  • To investigate the role of the NKCC1 co-transporter and its co-expression with ASCL3.
  • To assess the impact of interleukin (IL) instillation on tracheal electrophysiological properties.

Main Methods:

  • Ussing chamber technique with a custom tissue slider for precise mounting and recording.
  • Utilized Slc12a2-/- mice to study the Na-K-2Cl cotransporter 1 (NKCC1).
  • Employed a genetically modified mouse model for immunofluorescence to assess NKCC1 and ASCL3 co-expression.
  • Administered interleukins (ILs) to evaluate changes in fluid transport and mucus characteristics.

Main Results:

  • Proximal trachea showed higher anion secretion (cAMP- and succinate-induced) but no sodium absorption.
  • Distal trachea exhibited greater NBCe1-dependent bicarbonate and TMEM16A-dependent chloride secretion.
  • NKCC1+ cells, including those co-expressing ASCL3, were identified in submucosal glands and distal tracheal patches.
  • Interleukin treatment exclusively altered the electrophysiological properties of the distal trachea.

Conclusions:

  • The mouse trachea demonstrates differential regional organization of fluid transport functions.
  • Functional distribution of ion channels, transporters, and receptors underlies proximal-distal specialization.
  • The distal trachea exhibits plasticity in response to inflammatory stimuli (ILs), while the proximal trachea remains unaffected.