Brain endothelial cell TRPA1 channels initiate neurovascular coupling.

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  • Additional Information
    • Source:
      Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
    • Subject Terms:
      Cerebrovascular Circulation*; Arterioles/*metabolism ; Capillaries/*metabolism ; Endothelial Cells/*metabolism ; Neurovascular Coupling/*genetics ; TRPA1 Cation Channel/*genetics; Brain/metabolism ; TRPA1 Cation Channel/metabolism
    • Abstract:
      Cerebral blood flow is dynamically regulated by neurovascular coupling to meet the dynamic metabolic demands of the brain. We hypothesized that TRPA1 channels in capillary endothelial cells are stimulated by neuronal activity and instigate a propagating retrograde signal that dilates upstream parenchymal arterioles to initiate functional hyperemia. We find that activation of TRPA1 in capillary beds and post-arteriole transitional segments with mural cell coverage initiates retrograde signals that dilate upstream arterioles. These signals exhibit a unique mode of biphasic propagation. Slow, short-range intercellular Ca 2+ signals in the capillary network are converted to rapid electrical signals in transitional segments that propagate to and dilate upstream arterioles. We further demonstrate that TRPA1 is necessary for functional hyperemia and neurovascular coupling within the somatosensory cortex of mice in vivo. These data establish endothelial cell TRPA1 channels as neuronal activity sensors that initiate microvascular vasodilatory responses to redirect blood to regions of metabolic demand.
      Competing Interests: PT, MA, SA, AM, PP, EY, HP, BI, CT, SE No competing interests declared
      (© 2021, Thakore et al.)
    • Comments:
      Comment in: Cell Calcium. 2021 Jun;96:102407. (PMID: 33848732)
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    • Grant Information:
      RF1 NS110044 United States NS NINDS NIH HHS; P20 GM130459 United States GM NIGMS NIH HHS; K99 HL140106 United States HL NHLBI NIH HHS; P01 HL120840 United States HL NHLBI NIH HHS; R01 HL146054 United States HL NHLBI NIH HHS; R01 HL091905 United States HL NHLBI NIH HHS; R61 NS115132 United States NS NINDS NIH HHS; R01 HL137852 United States HL NHLBI NIH HHS; R35 HL155008 United States HL NHLBI NIH HHS; R01 HL137112 United States HL NHLBI NIH HHS; R01 HL139585 United States HL NHLBI NIH HHS
    • Contributed Indexing:
      Keywords: TRPA1 channels; conducted vasodilation; mouse; neuroscience; neurovascular coupling; panx1 channels; purinergic signaling
    • Accession Number:
      0 (TRPA1 Cation Channel)
      0 (Trpa1 protein, mouse)
    • Publication Date:
      Date Created: 20210226 Date Completed: 20220128 Latest Revision: 20220128
    • Publication Date:
      20221213
    • Accession Number:
      PMC7935492
    • Accession Number:
      10.7554/eLife.63040
    • Accession Number:
      33635784