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Neural activity drives dynamic Ca2+ signals in capillary endothelial cells that shape local brain blood flow
Author(s) -
Longden Thomas,
Harraz Osama,
Hennig Grant,
Shui Bo,
Lee Frank,
Lee Jane,
Reining Shaun,
Kotlikoff Michael,
Kostensis Evi,
König Gabriele,
HillEubanks David,
Nelson Mark
Publication year - 2019
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.2019.33.1_supplement.688.8
Subject(s) - chemistry , receptor , endoplasmic reticulum , biological neural network , microbiology and biotechnology , cerebral blood flow , pericyte , blood flow , neuroscience , biology , medicine , endothelial stem cell , in vitro , biochemistry
Brain capillaries constitute a vast, arborescent network of microscopic tubes composed of endothelial cells (ECs) that lie in close apposition to all neurons. Capillaries send long‐range electrical signals to regulate arteriolar diameter and control blood flowing into the brain, but it is unknown whether higher resolution control of blood flow exists within the capillary bed. Here, we demonstrate that capillary ECs exhibit recurrent, long‐lasting, high‐amplitude, local Ca 2+ signals in vivo that depend on neuronal activity. These signals are mediated by Gq‐protein‐coupled receptors, prominently including prostaglandin E 2 ‐induced activation of the EP 1 receptor, and reflect Ca 2+ release through endoplasmic reticulum IP 3 receptors and Ca 2+ entry through TRPV4 channels. EC Ca 2+ elevation at capillary branch points relaxes overlying pericytes, which is associated with a nitric oxide‐dependent increase in local blood flow. Capillary and arteriolar ECs respond robustly to neural stimulation, suggesting coordinated Ca 2+ signaling in these compartments directs blood flow to satisfy neuronal metabolic needs. Support or Funding Information Supported by American Heart Association postdoctoral fellowships and a Scientist Development Grant (14POST20480144; 17SDG33670237 to T.A.L.; 17POST33650030 to O.F.H), the Totman Medical Research Trust (to M.T.N.), Fondation Leducq (to M.T.N.), EC Horizon 2020 (to M.T.N.), and National Institutes of Health (NIH 4P20 GM103644/4‐5 to the Vermont Centre on Behavior and Health (T.A.L); P30‐GM‐103498 to the COBRE imaging facility at the University of Vermont College of Medicine; R24‐HL‐120847 to M.I.K; P01‐HL‐095488, R01‐HL‐121706, R37‐DK‐053832 and R01‐HL‐131181 to M.T.N., and FOR2372 to G.M.K and E.K). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .