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Purinergic signaling contributes to CO 2 ‐sensitivity of neurons in the retrotrapezoid nucleus but not nucleus of the solitary tract or medullary raphe (872.6)
Author(s) -
Wenker Ian,
Poss Erin,
Sobrinho Cleyton,
Ana Takakura,
Moreira Thiago,
Mulkey Daniel
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.872.6
Subject(s) - ppads , purinergic receptor , neuroscience , raphe nuclei , raphe , nucleus , solitary tract , purinergic signalling , serotonergic , dorsal raphe nucleus , biology , central chemoreceptors , chemoreceptor , chemistry , anatomy , endocrinology , control of respiration , receptor , respiration , serotonin , adenosine , agonist , adenosine receptor , biochemistry
Central chemoreception is the mechanism by which the brain controls breathing in response to changes in tissue CO2/H+. Several brainstem regions are thought to contribute to chemoreception including the caudal nucleus of the solitary tract (cNTS), medullary raphe and retrotrapezoid nucleus (RTN). Although the molecular basis of chemoreception remains unclear, evidence suggests that RTN chemoreception involves intrinsic H+ sensing by an unidentified K+ channel and purinergic signaling possibly from CO2‐sensitive astrocytes. However, it is not clear whether purinergic signaling influences CO2‐responsiveness of other putative chemoreceptors. The goal of this study is to determine whether purinergic signaling modulates basal activity or CO2‐responsivness of neurons in the cNTS or medullary raphe. We use cell‐attached current clamp techniques to characterize firing rate responses to 15% CO2 and focal application of ATP (1mM) under control conditions and in the presence of a P2‐receptor blocker (PPADS, 100 µM). Chemosensitive neurons in the cNTS or medullary raphe were identified in brain slices (300 µm thick) from neonatal rat pups (P7‐12) bases on a 蠅 0.5 Hz firing rate response to 15% CO2. We found that CO2‐sensitive neurons in the cNTS, but not the medullary raphe, respond to focal ATP application with ~3 fold increase in firing rate. However, bath application of PPADS had no effect on baseline activity or CO2‐responsivness of neurons in either region. Immunohistochemical analysis using an astrocyte‐specific marker (aldehyde dehydrogenase 1L1) suggests that the RTN has a higher density of astrocytes compared to the cNTS or medullary raphe. Together, these results suggest that purinergic signaling is a unique feature of RTN chemoreception. Grant Funding Source : Supported by NLBI (HL 104101) and AHA (11PRE7580037)