Brain endothelial cell trpa1 channels initiate neurovascular coupling

Pratish Thakore, Michael G. Alvarado, Sher Ali, Amreen Mughal, Paulo W. Pires, Evan Yamasaki, Harry A.T. Pritchard, Brant E. Isakson, Cam Ha T. Tran, Scott Earley

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 Ca2+ 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.

Original languageEnglish (US)
Article numbere63040
Pages (from-to)1-84
Number of pages84
JournaleLife
Volume10
DOIs
StatePublished - Feb 2021

Keywords

  • Conducted vasodilation
  • Neurovascular coupling
  • Panx1 channels
  • Purinergic signaling
  • TRPA1 channels

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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