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Shear Stress Potentiates the Activation of TRPV4 by GSK1016790A
Author(s) -
McIntyre Peter,
Baratchi Sara,
Almazi Juhura,
TovarLopez Francisco,
Darby William,
Mitchell Arnan
Publication year - 2015
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.29.1_supplement.714.5
Subject(s) - transient receptor potential channel , trpv4 , chemistry , shear stress , calcium in biology , calcium , intracellular , biophysics , microbiology and biotechnology , receptor , materials science , biochemistry , biology , composite material , organic chemistry
We assessed intracellular calcium levels ([Ca 2+ ] i ) in endothelial and HEK293 cells to study the effects of shear stress on the activation of Transient Receptor Potential Vanilloid 4 (TRPV4) by the agonist, GSK1016790A. TRPV4 is a calcium permeable ion channel that is activated by diverse stimuli, including shear stress. TRPV4 in endothelial cells can regulate flow‐mediated vascular tone. We have shown previously that TRPV4 responds to activation of GPCRs (1) and shear stress (2). Using a novel flow chamber and confocal Fluo 4 calcium imaging, we found that shear stress caused an increase in [Ca 2+ ] i mainly through TRPV4 (2) and potentiated responses to a TRPV4 agonist. We observed shear stress‐dependent recruitment of TRPV4 to the cell membrane. Disruption of exocytosis by inhibitors of clathrin‐ and dynamin‐dependent processes and disruption of actin, prevented this translocation. Inhibitors of the ILK‐Akt pathway also prevented TRPV4 translocation. TRPV4's role in the control of vascular tone and data from HEK293, bovine aortic endothelial and human umbilical vein endothelial cells is consistent with a potentiating effect of shear stress. We conclude that shear stress enhances TRPV4 responsiveness, at least in part, by increasing surface expression of TRPV4.