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PMID: 18378772 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 181 ·No. 1 ·2008-04-07 ·Pages 143-55

Fernandes J, Lorenzo IM, Andrade YN, Garcia-Elias A, Serra SA, Fernández-Fernández JM, Valverde MA

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 Terms
8,11,14-Eicosatrienoic Acid/analogs & derivatives,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,metabolism Phospholipases A2/metabolism TRPV Cation Channels/metabolism Temperature Type C Phospholipases/metabolism
Chemicals
Inositol 1,4,5-Trisphosphate Receptors TRPV Cation Channels 5,6-epoxy-8,11,14-eicosatrienoic acid Inositol 1,4,5-Trisphosphate Phospholipases A2 Type C Phospholipases 8,11,14-Eicosatrienoic Acid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Fernandes Jacqueline
Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain.
Lorenzo Ivan M
Andrade Yaniré N
Garcia-Elias Anna
Serra Selma A
Fernández-Fernández José M
Valverde Miguel A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200712058
Published
2008-04-07
Epub
2008-00-31
Pages
143-55
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2287294
Subset
IM
Corrections
ReprintIn
PMID: 18443356
External Links
PubMed source DOI: 10.1083/jcb.200712058 PMC Full Text View journal details
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