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The neuroepithelial body microenvironment as vagal mechanotransducer in intrapulmonary airways
Author(s) -
Lembrechts Robrecht,
Brouns Inge,
Schnorbusch Kathy,
Pintelon Isabel,
Timmermans Jean-Pierre,
Adriaensen Dirk
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.894.15
Subject(s) - microbiology and biotechnology , mechanotransduction , chemistry , vagus nerve , pulmonary stretch receptors , airway , lung , transient receptor potential channel , anatomy , receptor , neuroscience , biology , medicine , respiratory system , anesthesia , stimulation , biochemistry
Mechanical information collected by sensory nerve terminals in the airways is mainly conducted to the CNS by vagal myelinated nerve fibers. A majority of these terminals contacts densely innervated groups of neuroendocrine airway epithelial cells (neuroepithelial bodies; NEBs), prompting us to study the potential role of NEBs as key transducers of mechanical airway stimuli into activation of vagal sensory terminals. Mild hypo‐osmotic stimuli were used to study mechanosensitivity in a mouse lung slice model for live cell imaging (LCI) of NEBs, and evoked a selective Ca 2+ rise in NEB cells. Immunofluorescence and LCI showed that TRPC5, a Ca 2+ permeable hypo‐osmotically/mechanically gated TRP channel, was expressed on the apical membrane, and functionally involved in the osmomechanical activation and subsequent release of ATP by NEB cells. ATP may then activate ligand gated P2X 2/3 ATP receptors expressed by the terminals of myelinated vagal afferents in the NEB microenvironment. These terminals additionally expressed the inhibitory mechanogated K 2P channel TRAAK, likely serving a regulatory role in the indirect mechanical activation. The presented study characterized the NEB microenvironment as a functional unit for vagal airway mechanotransduction. Support: IWT fellowship SB/81162 (RL); FWO grants G.0081.08 (DA) and G.0589.11N (DA, JPT); UA grants GOA BOF 2007 (DA) and KP BOF 2006 (IB)