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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Purinergic signalling contributes to chemoreception in the retrotrapezoid nucleus but not the nucleus of the solitary tract or medullary raphe

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Sobrinho, Cleyton R. [1] ; Wenker, Ian C. [2] ; Poss, Erin M. [2] ; Takakura, Ana C. [3] ; Moreira, Thiago S. [1] ; Mulkey, Daniel K. [2]
Total Authors: 6
[1] Univ Sao Paulo, Dept Physiol & Biophys, BR-05508 Sao Paulo - Brazil
[2] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 - USA
[3] Univ Sao Paulo, Dept Pharmacol, BR-05508 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF PHYSIOLOGY-LONDON; v. 592, n. 6, p. 1309-1323, MAR 15 2014.
Web of Science Citations: 18

Key points Several brain regions are thought to sense changes in tissue CO2/H+ to regulate breathing (i.e. central chemoreceptors) including the nucleus of the solitary tract (NTS), medullary raphe and retrotrapezoid nucleus (RTN). Mechanism(s) underlying RTN chemoreception involve direct activation of RTN neurons by H+-mediated inhibition of a resting K+ conductance and indirect activation of RTN neurons by purinergic signalling, most likely from CO2/H+-sensitive astrocytes. Here, we confirm that activation of P2 receptors in the RTN stimulates cardiorespiratory activity, and we show at the cellular and systems level that purinergic signalling is not essential for CO2/H+ sensing in the NTS or medullary raphe. These results support the possibility that purinergic signalling is a unique feature of RTN chemoreception. Several brain regions are thought to function as important sites of chemoreception including the nucleus of the solitary tract (NTS), medullary raphe and retrotrapezoid nucleus (RTN). In the RTN, mechanisms of chemoreception involve direct H+-mediated activation of chemosensitive neurons and indirect modulation of chemosensitive neurons by purinergic signalling. Evidence suggests that RTN astrocytes are the source of CO2-evoked ATP release. However, it is not clear whether purinergic signalling also influences CO2/H+ responsiveness of other putative chemoreceptors. The goals of this study are to determine if CO2/H+-sensitive neurons in the NTS and medullary raphe respond to ATP, and whether purinergic signalling in these regions influences CO2 responsiveness in vitro and in vivo. In brain slices, cell-attached recordings of membrane potential show that CO2/H+-sensitive NTS neurons are activated by focal ATP application; however, purinergic P2-receptor blockade did not affect their CO2/H+ responsiveness. CO2/H+-sensitive raphe neurons were unaffected by ATP or P2-receptor blockade. In vivo, ATP injection into the NTS increased cardiorespiratory activity; however, injection of a P2-receptor blocker into this region had no effect on baseline breathing or CO2/H+ responsiveness. Injections of ATP or a P2-receptor blocker into the medullary raphe had no effect on cardiorespiratory activity or the chemoreflex. As a positive control we confirmed that ATP injection into the RTN increased breathing and blood pressure by a P2-receptor-dependent mechanism. These results suggest that purinergic signalling is a unique feature of RTN chemoreception. (AU)

FAPESP's process: 11/13462-7 - The interaction between retrotrapezoid nucleus astrocytes and neurons on respiratory responses promoted by central chemoreflex activation
Grantee:Cleyton Roberto Sobrinho
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 10/09776-3 - Neural mechanisms involved in expiratory rhythm generator: possible involvement of the retrotrapezoid nucleus and the parafacial region
Grantee:Ana Carolina Thomaz Takakura
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 10/19336-0 - Pontine mechanisms involved in cardiorespiratory control during central or peripheral chemoreceptors activation
Grantee:Thiago dos Santos Moreira
Support type: Regular Research Grants