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P2Y1‐receptors are expressed by CO2/H+‐insensitive neurons in the retrotrapezoid nucleus (RTN) and contribute to the peripheral drive to breathe
Author(s) -
Wenker Ian Christopher,
Takakura Ana,
Moreira Thiago,
Mulkey Daniel Kent
Publication year - 2012
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.26.1_supplement.894.2
Subject(s) - chemoreceptor , peripheral chemoreceptors , central chemoreceptors , receptor , in vivo , electrophysiology , agonist , neuroscience , antagonist , biology , medicine , endocrinology , chemistry , pharmacology , microbiology and biotechnology
The chemical drive to breathe comes from central chemoreceptors that sense tissue CO 2 /H + , and peripheral chemoreceptors that sense arterial CO 2 /H + and O 2 . Changes in CO 2 /H + and O 2 can trigger ATP release near the RTN, and ATP has been shown to modulate activity of RTN neurons, possibly by activation of P2Y1‐receptors (P2Y1‐R). Therefore, we hypothesize that P2Y1‐R represent the molecular basis for central and peripheral chemoreceptor integration at the level of the RTN. Here, we use in vivo and in vitro recording techniques to examine the role of P2Y1‐R expressed by RTN neurons in central and peripheral chemoreception. In vivo , bilateral injection of MRS2365, a P2Y1‐R specific agonist, into the RTN of anesthetized adult rats increased phrenic nerve amplitude 24% and frequency 31%, whereas application of the specific P2Y1‐R antagonist MRS2179 decreased the ventilatory response to peripheral chemoreceptor activation but not hypercapnia. In vitro , loose‐patch recordings of neurons in slices from rats (P7–12) show that baseline activity and CO 2 /H + ‐sensitivity of chemoreceptors was unaffected by MRS2179 or MRS2365. Conversely, MRS2179 decreased baseline activity of non‐chemosensitive RTN neurons by 42 % and MRS2365 increased activity of these cells by 630 %. These results indicate that P2Y1‐R are functionally expressed in nonchemosensitive RTN neurons and contribute to peripheral chemoreception.