title: Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium: involvement of TRPC5.
abstract: In rodent lungs, a major part of the myelinated vagal airway afferents selectively contacts pulmonary neuroepithelial bodies (NEBs). Because 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. 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 hypoosmotic 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 hypoosmotic stimuli (< 200 mosmol). NEB cells selectively expressed the Ca(2+)-permeable osmo- and mechanosensitive transient receptor potential canonical channel 5 (TRPC5) in their apical membranes, whereas immunoreactivity for TRP vanilloid-4 and TRP melastatin-3 was abundant in virtually all other airway epithelial cells. Hypoosmotic 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 the release of ATP from NEB cells. Because 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 central nervous system via a purinergic signaling pathway.
authors.affiliation: Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Groenenborgerlaan 171, BE-2020 Antwerp, Belgium.
authors.forename: Robrecht
authors.initials: R
authors.lastname: Lembrechts
authors.forename: Inge
authors.initials: I
authors.lastname: Brouns
authors.forename: Kathy
authors.initials: K
authors.lastname: Schnorbusch
authors.forename: Isabel
authors.initials: I
authors.lastname: Pintelon
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
authors.forename: Dirk
authors.initials: D
authors.lastname: Adriaensen
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D046568:Neuroepithelial Bodies; D009995:Osmosis
chemical_list: D007473:Ion Channels; D002118:Calcium