title: TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity.
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 A(2)-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 4alpha-phorbol 12,13-didecanoate increased cationic currents, intracellular Ca(2+), 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 Ca(2+) signal required for the autoregulation of CBF.
authors.affiliation: Grup de Fisiologia Cellular i Molecular, Unitat de Senyalització Cellular, Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Yaniré N
authors.initials: YN
authors.lastname: Andrade
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fernandes
authors.forename: Esther
authors.initials: E
authors.lastname: Vázquez
authors.forename: José M
authors.initials: JM
authors.lastname: Fernández-Fernández
authors.forename: Maite
authors.initials: M
authors.lastname: Arniges
authors.forename: Trinidad M
authors.initials: TM
authors.lastname: Sánchez
authors.forename: Manuel
authors.initials: M
authors.lastname: Villalón
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valverde
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology*; D006224:Cricetinae; D003600:Cytosol / Q000737:chemistry; D003911:Dextrans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005187:Fallopian Tubes / Q000166:cytology; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008024:Ligands; D040542:Mechanotransduction, Cellular; D008647:Mesocricetus; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D050916:TRPV Cation Channels; D013997:Time Factors; D014783:Viscosity
chemical_list: D027682:Cation Transport Proteins; D003911:Dextrans; D007473:Ion Channels; D008024:Ligands; D010703:Phorbol Esters; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; C008876:phorbol-12,13-didecanoate; D005682:Gadolinium; D010741:Phospholipases A; D002118:Calcium