Robrecht Lembrechts, Inge Brouns, Kathy Schnorbusch, Isabel Pintelon, Jean-Pierre Timmermans, Dirk Adriaensen

, 2012 Mar 29 , ,

In rodent lungs, a major part of the myelinated vagal airway afferents selectively contacts pulmonary neuroepithelial bodies (NEBs). Since most myelinated vagal airway afferents concern physiologically characterized mechanoreceptors, the present study aimed at unraveling the potential involvement of NEB cells in transducing mechanosensory information from the airways to the central nervous system (CNS). Physiological studies were performed using confocal Ca(2+) imaging of airway epithelium in murine lung slices. 'Mechanical' stimulation by short term application of a mild hypo-osmotic solution (230 mosmol) resulted in a selective, fast, reversible and reproducible Ca(2+) rise in NEB cells. Other airway epithelial cells could only be activated using more severe hypo-osmotic stimuli (<200 mosmol). NEB cells selectively expressed the Ca(2+) permeable osmo- and mechanosensitive TRP channel TRPC5 in their apical membranes, while immunoreactivity for TRPV4 and TRPM3 was abundant in virtually all other airway epithelial cells. Hypo-osmotic activation of NEB cells was prevented by GsMTx-4, an inhibitor of mechanosensitive ion channels, and by SKF96365, an inhibitor of TRPC channels. Short application of gadolinium, reported to activate TRPC5 channels, evoked a transient Ca(2+) rise in NEB cells. Osmomechanical activation of NEB cells gave rise to a typical delayed activation of Clara-like cells, due to release of ATP from NEB cells. Since ATP may activate the NEB-associated P2X(2/3) ATP receptor expressing myelinated vagal afferents, the current observations strongly suggest that pulmonary NEB cells are fully equipped to initiate mechanosensory signal transduction to the CNS via a purinergic signaling pathway.