Functional Differences in Electrolyte Transport Between the Mouse Proximal and Distal Trachea

The mammalian tracheal epithelium is composed of different cell types distributed along the proximal-distal axis. Nevertheless, variations in expression and function of ion channels and transporters participating in fluid absorption and secretion have never been studied separately in proximal and distal mouse trachea. This work aims to characterize basal and stimulated absorption and secretion of fluid obtained from proximal and distal trachea from the same animal.

Ussing chamber was performed using a custom-made tissue slider allowing small tracheal sections mounting, where response to agonists and blockers was recorded. The role of NKCC1 co-transporter was studied using the Slc12a2^-/- mouse. A genetically tomato-induced mouse model was used to assess co-expression of NKCC1 and ASCL3 by immunofluorescence. Animals were instilled with interleukins (ILs) to determine changes in absorption, secretion, and mucus properties.

Proximal trachea didn't participate in sodium absorption but exhibited higher cAMP- and succinate-induced anion secretion than the distal section. NBCe1-dependent bicarbonate and TMEM16A-driven chloride secretion were significantly higher in distal trachea. NKCC1+ cells were found in the submucosal glands (SMGs) and abundant patches of NKCC1+ cells in the distal region. Isolated NKCC1+ cells co-expressing ASCL3 were also detected. ILs treatment changed the electrophysiological properties of the distal trachea exclusively.

Our experiments determined that the mouse trachea organizes its functions differentially in proximal and distal regions, based on the functional distribution of channels, transporters, and receptors. While the distal trachea changed its responses to agonists inducing anion secretion, the proximal trachea was unperturbed by ILs addition.