Author
Cleary, Colin M.Moreira, Thiago S.
Takakura, Ana C.
Nelson, Mark T.
Longden, Thomas A.
Mulkey, Daniel K.
Date
2020-09-14Journal
eLifePublisher
eLife Sciences PublicationsType
Article
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Show full item recordAbstract
Respiratory chemoreceptors regulate breathing in response to changes in tissue CO2/ H+. Blood flow is a fundamental determinant of tissue CO2/H+, yet little is known regarding how regulation of vascular tone in chemoreceptor regions contributes to respiratory behavior. Previously, we showed in rat that CO2/H+-vasoconstriction in the retrotrapezoid nucleus (RTN) supports chemoreception by a purinergic-dependent mechanism (Hawkins et al., 2017). Here, we show in mice that CO2/H+ dilates arterioles in other chemoreceptor regions, thus demonstrating CO2/H+ vascular reactivity in the RTN is unique. We also identify P2Y2 receptors in RTN smooth muscle cells as the substrate responsible for this response. Specifically, pharmacological blockade or genetic deletion of P2Y2 from smooth muscle cells blunted the ventilatory response to CO2, and re-expression of P2Y2 receptors only in RTN smooth muscle cells fully rescued the CO2/H+ chemoreflex. These results identify P2Y2 receptors in RTN smooth muscle cells as requisite determinants of respiratory chemoreception.Sponsors
American Heart AssociationKeyword
astrocytechemoreception
functional vascular heterogeneity
mouse
neuroscience
neurovascular unit
retrotrapezoid nucleus
Identifier to cite or link to this item
http://hdl.handle.net/10713/13884ae974a485f413a2113503eed53cd6c53
10.7554/eLife.59499
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