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Molecular and physiological evidence for neuroepithelial bodies (NEBs) as mechanotransducers in the intrapulmonary airway epithelium
Author(s) -
Lembrechts Robrecht,
Brouns Inge,
Schnorbusch Kathy,
Pintelon Isabel,
Timmermans JeanPierre,
Adriaensen Dirk
Publication year - 2011
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.25.1_supplement.659.9
NEBs are diffusely spread groups of extensively innervated neuroendocrine cells in the airway epithelium. Because NEB cells are associated with myelinated vagal afferents that express a mechanosensory neurochemical coding (e.g. P2X 2/3 ATP receptors), the present study was designed to find evidence for NEBs as airway mechanotransducers. Application of hypo‐osmotic stimuli (230 mOsm) to a mouse lung vibratome slice model for live cell imaging of NEBs, revealed a selective increase in intracellular Ca 2+ in NEB cells and consecutive exocytosis of ATP. Immunofluorescence of mouse lung cryosections showed the expression of TRPC5, a Ca 2+ permeable hypo‐osmotically and mechanically gated channel, on the apical membrane of NEB cells. The hypo‐osmotic activation of NEB cells in lung slices was prevented by GsMTx‐4 (5 μM), a toxin that blocks TRPC5. Gadolinium (500 μM), reported to activate TRPC5 channels, evoked a Ca 2+ rise in NEB cells. In conclusion, NEB cells revealed a pathway for hypo‐osmotic/mechanical activation via TRPC5, resulting in a Ca 2+ rise and exocytosis of ATP. These data confirm the potential role of NEBs as airway mechanotransducers, able to activate the NEB‐associated P2X 2/3 ATP receptor expressing myelinated vagal afferents upon mechanical stimulation. Support: IWT fellowship SB/81162 (RL); FWO grant G.0081.08 (DA, IB); UA grant GOA BOF 2007 (DA)