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Endothelial Ca 2+ signals in Penetrating Arterioles Control Local Blood Flow in the Brain.
Author(s) -
Mughal Amreen,
Longden Thomas,
Hennig Grant W.,
Nelson Mark T.
Publication year - 2020
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.2020.34.s1.04433
Subject(s) - trpv4 , endothelium , microbiology and biotechnology , cerebral circulation , receptor , neuroscience , chemistry , endoplasmic reticulum , cerebral blood flow , stimulation , cerebral arteries , microcirculation , perfusion , anatomy , biology , transient receptor potential channel , medicine , endocrinology , biochemistry
Cerebral blood flow is exquisitely regulated to meet the fluctuating demands of active neurons. This activity‐dependent increase in blood flow (functional hyperemia) is managed by a number of molecular mechanisms collectively referred to as ‘neurovascular coupling’. Penetrating arterioles—the bridge between pial arteries and deep capillaries—serve as a high‐level control system to regulate local perfusion into the cortex. Here we show that dynamic Ca 2+ signals in arteriolar endothelium, consisting of unitary and compound events with distinct spatiotemporal patterning, are dramatically increased by sensory stimulation and are followed by dilation of upstream arterioles and increased RBC flux in downstream capillaries. These arteriolar endothelial Ca 2+ signals in the cortical vasculature are dependent on G q ‐protein coupled receptor signaling likely involving prostaglandin E 2 (PGE 2 ). PGE2‐dependent activation of EP1 receptors, results in IP 3 receptor‐dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry via TRPV4 channels. Our data highlight the pivotal role of endothelial Ca 2+ signals in the regulation of cerebral blood flow. Support or Funding Information Supported by the National Institutes of Health, Totman Medical Research Trust, Fondation Leducq, EC Horizon 2020.