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Published online 7 March 2005. doi:10.1083/jcb.200409070
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 6, 869-874
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TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity

Yaniré N. Andrade1,2, Jacqueline Fernandes1, Esther Vázquez1, José M. Fernández-Fernández1, Maite Arniges1, Trinidad M. Sánchez2, Manuel Villalón2, and Miguel A. Valverde1

1 Grup de Fisiologia Cel·lular i Molecular, Unitat de Senyalització Cel·lular, Universitat Pompeu Fabra, Barcelona 08003, Spain
2 Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

Correspondence to M.A. Valverde: miguel.valverde{at}upf.edu


Abstract
Autoregulation of the ciliary beat frequency (CBF) has been proposed as the mechanism used by epithelial ciliated cells to maintain the CBF and prevent the collapse of mucociliary transport under conditions of varying mucus viscosity. Despite the relevance of this regulatory response to the pathophysiology of airways and reproductive tract, the underlying cellular and molecular aspects remain unknown. Hamster oviductal ciliated cells express the transient receptor potential vanilloid 4 (TRPV4) channel, which is activated by increased viscous load involving a phospholipase A2–dependent pathway. TRPV4-transfected HeLa cells also increased their cationic currents in response to high viscous load. This mechanical activation is prevented in native ciliated cells loaded with a TRPV4 antibody. Application of the TRPV4 synthetic ligand 4{alpha}-phorbol 12,13-didecanoate increased cationic currents, intracellular Ca2+, and the CBF in the absence of a viscous load. Therefore, TRPV4 emerges as a candidate to participate in the coupling of fluid viscosity changes to the generation of the Ca2+ signal required for the autoregulation of CBF.

Abbreviations used in this paper: 4{alpha}PDD, 4{alpha}-phorbol 12,13-didecanoate; AACOCF3, arachidonyl trifluoromethyl ketone; CBF, ciliary beat frequency; NMDG, N-methyl-D-glucamine; pBPB, 4-bromophenacyl bromide; PLA2, phospholipase A2; TRPV4, transient receptor potential vanilloid 4.


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