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  1. Article ; Online: IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acid.

    Fernandes, Jacqueline / Lorenzo, Ivan M / Andrade, Yaniré N / Garcia-Elias, Anna / Serra, Selma A / Fernández-Fernández, José M / Valverde, Miguel A

    The Journal of general physiology

    2008  Volume 131, Issue 5, Page(s) i2

    Abstract: Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A2 (PLA2) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show ... ...

    Abstract Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A2 (PLA2) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show that both high viscous loading and hypotonicity stimuli in native ciliated epithelial cells use PLA2-EET as the primary pathway to activate TRPV4. Under conditions of low PLA2 activation, both also use extracellular ATP-mediated activation of phospholipase C (PLC)-inositol trisphosphate (IP3) signaling to support TRPV4 gating. IP3, without being an agonist itself, sensitizes TRPV4 to EET in epithelial ciliated cells and cells heterologously expressing TRPV4, an effect inhibited by the IP3 receptor antagonist xestospongin C. Coimmunoprecipitation assays indicated a physical interaction between TRPV4 and IP3 receptor 3. Collectively, our study suggests a functional coupling between plasma membrane TRPV4 channels and intracellular store Ca2+ channels required to initiate and maintain the oscillatory Ca2+ signal triggered by high viscosity and hypotonic stimuli that do not reach a threshold level of PLA2 activation.
    Language English
    Publishing date 2008-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3118-5
    ISSN 1540-7748 ; 0022-1295
    ISSN (online) 1540-7748
    ISSN 0022-1295
    DOI 10.1085/JGP1315OIA2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Functional coupling of TRPV4 cationic channel and large conductance, calcium-dependent potassium channel in human bronchial epithelial cell lines.

    Fernández-Fernández, José M / Andrade, Yaniré N / Arniges, Maite / Fernandes, Jacqueline / Plata, Cristina / Rubio-Moscardo, Francisca / Vázquez, Esther / Valverde, Miguel A

    Pflugers Archiv : European journal of physiology

    2008  Volume 457, Issue 1, Page(s) 149–159

    Abstract: Calcium-dependent potassium channels are implicated in electrolyte transport, cell volume regulation and mechanical responses in epithelia, although the pathways for calcium entry and their coupling to the activation of potassium channels are not fully ... ...

    Abstract Calcium-dependent potassium channels are implicated in electrolyte transport, cell volume regulation and mechanical responses in epithelia, although the pathways for calcium entry and their coupling to the activation of potassium channels are not fully understood. We now show molecular evidence for the presence of TRPV4, a calcium permeable channel sensitive to osmotic and mechanical stress, and its functional coupling to the large conductance calcium-dependent potassium channel (BK(Ca)) in a human bronchial epithelial cell line (HBE). Reverse transcriptase polymerase chain reaction, intracellular calcium imaging and whole-cell patch-clamp experiments using HBE cells demonstrated the presence of TRPV4 messenger and Ca(2+) entry, and outwardly rectifying cationic currents elicited by the TRPV4 specific activator 4alpha-phorbol 12,13-didecanoate (4alphaPDD). Cell-attached and whole-cell patch-clamp of HBE cells exposed to 4alphaPDD, and hypotonic and high-viscosity solutions (related to mechanical stress) revealed the activation of BK(Ca) channels subsequent to extracellular Ca(2+) influx via TRPV4, an effect lost upon antisense-mediated knock-down of TRPV4. Further analysis of BK(Ca) modulation after TRPV4 activation showed that the Ca(2+) signal can be generated away from the BK(Ca) location at the plasma membrane, and it is not mediated by intracellular Ca(2+) release via ryanodine receptors. Finally, we have shown that, unlike the reported disengagement of TRPV4 and BK(Ca) in response to hypotonic solutions, cystic fibrosis bronchial epithelial cells (CFBE) preserve the functional coupling of TRPV4 and BK(Ca) in response to high-viscous solutions.
    MeSH term(s) Bronchi/cytology ; Bronchi/physiology ; Cell Line ; Cystic Fibrosis/pathology ; Electrophysiology ; Epithelial Cells/physiology ; Humans ; Hypotonic Solutions/pharmacology ; Large-Conductance Calcium-Activated Potassium Channels/physiology ; Oligoribonucleotides, Antisense/pharmacology ; Osmotic Pressure ; Phorbol Esters/pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; TRPV Cation Channels/physiology ; Viscosity
    Chemical Substances Hypotonic Solutions ; Large-Conductance Calcium-Activated Potassium Channels ; Oligoribonucleotides, Antisense ; Phorbol Esters ; TRPV Cation Channels ; TRPV4 protein, human ; phorbol-12,13-didecanoate (24928-17-4)
    Language English
    Publishing date 2008-05-06
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-008-0516-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acid.

    Fernandes, Jacqueline / Lorenzo, Ivan M / Andrade, Yaniré N / Garcia-Elias, Anna / Serra, Selma A / Fernández-Fernández, José M / Valverde, Miguel A

    The Journal of cell biology

    2008  Volume 181, Issue 1, Page(s) 143–155

    Abstract: Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A(2) (PLA(2)) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We ... ...

    Abstract Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A(2) (PLA(2)) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show that both high viscous loading and hypotonicity stimuli in native ciliated epithelial cells use PLA(2)-EET as the primary pathway to activate TRPV4. Under conditions of low PLA(2) activation, both also use extracellular ATP-mediated activation of phospholipase C (PLC)-inositol trisphosphate (IP(3)) signaling to support TRPV4 gating. IP(3), without being an agonist itself, sensitizes TRPV4 to EET in epithelial ciliated cells and cells heterologously expressing TRPV4, an effect inhibited by the IP(3) receptor antagonist xestospongin C. Coimmunoprecipitation assays indicated a physical interaction between TRPV4 and IP(3) receptor 3. Collectively, our study suggests a functional coupling between plasma membrane TRPV4 channels and intracellular store Ca(2+) channels required to initiate and maintain the oscillatory Ca(2+) signal triggered by high viscosity and hypotonic stimuli that do not reach a threshold level of PLA(2) activation.
    MeSH term(s) 8,11,14-Eicosatrienoic Acid/analogs & derivatives ; 8,11,14-Eicosatrienoic Acid/metabolism ; Animals ; Calcium Signaling ; Cricetinae ; Female ; HeLa Cells ; Humans ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Mechanotransduction, Cellular ; Osmosis ; Oviducts/cytology ; Oviducts/metabolism ; Phospholipases A2/metabolism ; TRPV Cation Channels/metabolism ; Temperature ; Type C Phospholipases/metabolism
    Chemical Substances Inositol 1,4,5-Trisphosphate Receptors ; TRPV Cation Channels ; 5,6-epoxy-8,11,14-eicosatrienoic acid (81246-84-6) ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; Phospholipases A2 (EC 3.1.1.4) ; Type C Phospholipases (EC 3.1.4.-) ; 8,11,14-Eicosatrienoic Acid (FC398RK06S)
    Language English
    Publishing date 2008-03-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.200712058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: IP₃ sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5'-6'-epoxyeicosatrienoic acid

    Fernandes, Jacqueline / Lorenzo, Ivan M / Andrade, Yaniré N / Garcia-Elias, Anna / Serra, Selma A / Fernández-Fernández, José M / Valverde, Miguel A

    Journal of cell biology. 2008 Apr. 7, v. 181, no. 1

    2008  

    Abstract: Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A₂ (PLA₂) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show ... ...

    Abstract Mechanical and osmotic sensitivity of the transient receptor potential vanilloid 4 (TRPV4) channel depends on phospholipase A₂ (PLA₂) activation and the subsequent production of the arachidonic acid metabolites, epoxyeicosatrienoic acid (EET). We show that both high viscous loading and hypotonicity stimuli in native ciliated epithelial cells use PLA₂-EET as the primary pathway to activate TRPV4. Under conditions of low PLA₂ activation, both also use extracellular ATP-mediated activation of phospholipase C (PLC)-inositol trisphosphate (IP₃) signaling to support TRPV4 gating. IP₃, without being an agonist itself, sensitizes TRPV4 to EET in epithelial ciliated cells and cells heterologously expressing TRPV4, an effect inhibited by the IP₃ receptor antagonist xestospongin C. Coimmunoprecipitation assays indicated a physical interaction between TRPV4 and IP₃ receptor 3. Collectively, our study suggests a functional coupling between plasma membrane TRPV4 channels and intracellular store Ca²⁺ channels required to initiate and maintain the oscillatory Ca²⁺ signal triggered by high viscosity and hypotonic stimuli that do not reach a threshold level of PLA₂ activation.
    Language English
    Dates of publication 2008-0407
    Size p. 143-155.
    Publishing place The Rockefeller University Press
    Document type Article
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity.

    Andrade, Yaniré N / Fernandes, Jacqueline / Vázquez, Esther / Fernández-Fernández, José M / Arniges, Maite / Sánchez, Trinidad M / Villalón, Manuel / Valverde, Miguel A

    The Journal of cell biology

    2005  Volume 168, Issue 6, Page(s) 869–874

    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 ... ...

    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.
    MeSH term(s) Animals ; Blotting, Western ; Calcium/metabolism ; Cation Transport Proteins/genetics ; Cation Transport Proteins/physiology ; Cells, Cultured ; Cilia/physiology ; Cricetinae ; Cytosol/chemistry ; Dextrans/pharmacology ; Dose-Response Relationship, Drug ; Epithelial Cells/cytology ; Epithelial Cells/physiology ; Fallopian Tubes/cytology ; Female ; Gadolinium/pharmacology ; HeLa Cells ; Humans ; Ion Channels/genetics ; Ion Channels/physiology ; Kinetics ; Ligands ; Mechanotransduction, Cellular ; Mesocricetus ; Microscopy, Confocal ; Patch-Clamp Techniques ; Phorbol Esters/pharmacology ; Phospholipases A/metabolism ; TRPV Cation Channels ; Time Factors ; Viscosity
    Chemical Substances Cation Transport Proteins ; Dextrans ; Ion Channels ; Ligands ; Phorbol Esters ; TRPV Cation Channels ; TRPV4 protein, human ; phorbol-12,13-didecanoate (24928-17-4) ; Gadolinium (AU0V1LM3JT) ; Phospholipases A (EC 3.1.1.32) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2005-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.200409070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity

    Andrade, Yaniré N / Fernandes, Jacqueline / Vázquez, Esther / Fernández-Fernández, José M / Arniges, Maite / Sánchez, Trinidad M / Villalón, Manuel / Valverde, Miguel A

    Journal of cell biology. 2005 Mar. 14, v. 168, no. 6

    2005  

    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 ... ...

    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.
    Language English
    Dates of publication 2005-0314
    Size p. 869-874.
    Document type Article
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    Database NAL-Catalogue (AGRICOLA)

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