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    The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

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    Author
    Hariharan, A.
    Weir, N.
    Robertson, C.
    He, L.
    Betsholtz, C.
    Longden, T.A.
    Date
    2020-12-18
    Journal
    Frontiers in Cellular Neuroscience
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fncel.2020.601324
    Abstract
    Brain pericytes reside on the abluminal surface of capillaries, and their processes cover ~90% of the length of the capillary bed. These cells were first described almost 150 years ago (Eberth, 1871; Rouget, 1873) and have been the subject of intense experimental scrutiny in recent years, but their physiological roles remain uncertain and little is known of the complement of signaling elements that they employ to carry out their functions. In this review, we synthesize functional data with single-cell RNAseq screens to explore the ion channel and G protein-coupled receptor (GPCR) toolkit of mesh and thin-strand pericytes of the brain, with the aim of providing a framework for deeper explorations of the molecular mechanisms that govern pericyte physiology. We argue that their complement of channels and receptors ideally positions capillary pericytes to play a central role in adapting blood flow to meet the challenge of satisfying neuronal energy requirements from deep within the capillary bed, by enabling dynamic regulation of their membrane potential to influence the electrical output of the cell. In particular, we outline how genetic and functional evidence suggest an important role for Gs-coupled GPCRs and ATP-sensitive potassium (KATP) channels in this context. We put forth a predictive model for long-range hyperpolarizing electrical signaling from pericytes to upstream arterioles, and detail the TRP and Ca2+ channels and Gq, Gi/o, and G12/13 signaling processes that counterbalance this. We underscore critical questions that need to be addressed to further advance our understanding of the signaling topology of capillary pericytes, and how this contributes to their physiological roles and their dysfunction in disease. Copyright Copyright Copyright 2020 Hariharan, Weir, Robertson, He, Betsholtz and Longden.
    Sponsors
    Support for this work was provided by the NIH National Institute on Aging and National Institute of Neurological Disorders and Stroke (1R01AG066645 and 1DP2NS121347, to TL), the American Heart Association (17SDG33670237 and 19IPLOI34660108 to TL), and the Swedish Cancer Society (to CB).
    Keyword
    brain metabolism
    cerebral blood flow (CBF)
    GPCRs (G protein coupled receptors)
    ion channels
    KATP channels
    neurovascular coupling (NVC)
    pericytes
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14528
    ae974a485f413a2113503eed53cd6c53
    10.3389/fncel.2020.601324
    Scopus Count
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