VTechWorks staff will be away for the Thanksgiving holiday beginning at noon on Wednesday, November 27, through Friday, November 29. We will resume normal operations on Monday, December 2. Thank you for your patience.
 

Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus

Simple item page
dc.contributor.authorJames, S. D.en
dc.contributor.authorHawkins, V. E.en
dc.contributor.authorFalquetto, B.en
dc.contributor.authorRuskin, D. N.en
dc.contributor.authorMasino, S. A.en
dc.contributor.authorMoreira, T. S.en
dc.contributor.authorOlsen, Michelle L.en
dc.contributor.authorMulkey, D. K.en
dc.contributor.departmentSchool of Neuroscienceen
dc.date.accessioned2019-02-22T14:23:37Zen
dc.date.available2019-02-22T14:23:37Zen
dc.date.issued2018en
dc.description.abstractA subset of neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating depth and frequency of breathing in response to changes in tissue CO2/H. The activity of chemosensitive RTN neurons is also subject to modulation by CO2/H-dependent purinergic signaling. However, mechanisms contributing to purinergic regulation of RTN chemoreceptors are not entirely clear. Recent evidence suggests adenosine inhibits RTN chemoreception in vivo by activation of A1 receptors. The goal of this study was to characterize effects of adenosine on chemosensitive RTN neurons and identify intrinsic and synaptic mechanisms underlying this response. Cell-attached recordings from RTN chemoreceptors in slices from rat or wild-type mouse pups (mixed sex) show that exposure to adenosine (1 M) inhibits chemoreceptor activity by an A1 receptor-dependent mechanism. However, exposure to a selective A1 receptor antagonist (8-cyclopentyl-1,3- dipropylxanthine, DPCPX; 30 nM) alone did not potentiate CO2/H-stimulated activity, suggesting activation of A1 receptors does not limit chemoreceptor activity under these reduced conditions. Whole-cell voltage-clamp from chemosensitive RTN neurons shows that exposure to adenosine activated an inward rectifying K conductance, and at the network level, adenosine preferentially decreased frequency of EPSCs but not IPSCs. These results show that adenosine activation of A1 receptors inhibits chemosensitive RTN neurons by direct activation of a G-protein-regulated inward-rectifier K (GIRK)-like conductance, and presynaptically, by suppression of excitatory synaptic input to chemoreceptors.en
dc.description.sponsorshipThis work was supported by National Institutes of Health Grants HL104101 (to D.K.M., M.L.O.), HL137094 (to D.K.M.), NS065957 (to S.A.M.), NS066392 (to S.A.M.), and AT008742 (to D.N.R.). Additional funds were also provided by the Dravet Foundation Grant AG180243 (to D.K.M.), the São Paulo Research Foundation Grants 2014/04866-5 (to B.F.), 2015/23376-1 (to T.S.M.), 2016/ 22069-0 (to T.S.M.), and Trinity College (S.A.M., D.N.R.).en
dc.format.extent11 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1523/ENEURO.0404-18.2018en
dc.identifier.urihttp://hdl.handle.net/10919/87739en
dc.language.isoen_USen
dc.publisherSociety for Neuroscienceen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectbrain sliceen
dc.subjectcellularen
dc.subjectchemoreceptionen
dc.subjectnetworken
dc.subjectRTNen
dc.titleAdenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleusen
dc.title.serialeNeuroen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ENEURO.0404-18.2018.pdf
Size:
2.15 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Scholarly Works, School of Neuroscience