Show simple item record

dc.contributor.authorJames, S.D.
dc.contributor.authorHawkins, V.E.
dc.contributor.authorFalquetto, B.
dc.contributor.authorRuskin, D.N.
dc.contributor.authorMasino, S.A.
dc.contributor.authorMoreira, T.S.
dc.contributor.authorOlsen, M.L.
dc.contributor.authorMulkey, D.K.
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_US
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.).
dc.format.extent11 pages
dc.publisherSociety for Neuroscience
dc.rightsCreative Commons Attribution 4.0 International
dc.subjectbrain slice
dc.titleAdenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleusen_US
dc.typeArticle - Refereed

Files in this item


This item appears in the following Collection(s)

Show simple item record

Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International