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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
Autor(es):
James, S. D. [1] ; Hawkins, V. E. [1] ; Falquetto, B. [2, 1] ; Ruskin, D. N. [3] ; Masino, S. A. [3] ; Moreira, T. S. [4] ; Olsen, M. L. [5] ; Mulkey, D. K. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 - USA
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
[3] Trinity Coll Hartford, Dept Psychol, Neurosci Program, Hartford, CT - USA
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
[5] Virginia Polytech Inst & State Univ, Sch Neurosci, Blacksburg, VA 24061 - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: ENEURO; v. 5, n. 6 NOV-DEC 2018.
Citações Web of Science: 2
Resumo

A 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 Al 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 mu M) inhibits chennoreceptor activity by an Al receptor-dependent mechanism. However, exposure to a selective Al receptor antagonist (8-cyclopentyL-1,3-dipropylxanthine, DPCPX; 30 nM) alone did not potentiate CO2/H+-stimulated activity, suggesting activation of Al receptors does not limit chennoreceptor 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 Al 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. (AU)

Processo FAPESP: 14/04866-5 - Participação dos receptores P2Y1 dos neurônios C1 do bulbo ventrolateral rostral no controle cardiorrespiratório
Beneficiário:Bárbara Falquetto
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
Beneficiário:Thiago dos Santos Moreira
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/22069-0 - Melhora nos mecanismos de regulação do fluxo sanguíneo encefálico em animais espontaneamente hipertensos: participação do exercício físico
Beneficiário:Thiago dos Santos Moreira
Modalidade de apoio: Auxílio à Pesquisa - Regular