Brain endothelial cell TRPA1 channels initiate neurovascular coupling

Author:

Thakore Pratish1ORCID,Alvarado Michael G1ORCID,Ali Sher1,Mughal Amreen2ORCID,Pires Paulo W3ORCID,Yamasaki Evan1,Pritchard Harry AT14,Isakson Brant E56,Tran Cam Ha T7,Earley Scott1ORCID

Affiliation:

1. Department of Pharmacology, Center for Molecular and Cellular Signaling in the Cardiovascular System, University of Nevada, Reno School of Medicine, Reno, United States

2. Department of Pharmacology, College of Medicine, University of Vermont, Burlington, United States

3. Department of Physiology, College of Medicine, University of Arizona, Tucson, United States

4. Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom

5. Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States

6. Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, United States

7. Department of Physiology & Cell Biology, Center for Molecular and Cellular Signaling in the Cardiovascular System, University of Nevada, Reno School of Medicine, Reno, United States

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.

Funder

National Heart, Lung, and Blood Institute

National Institute of Neurological Disorders and Stroke

National Institute of General Medical Sciences

American Heart Association

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference45 articles.

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