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Potent excitation of inspiratory frequency by P2Y 1 receptor activation in the preBotzinger complex (PBC)
Author(s) -
Lorier Amanda Ruth,
Huxtable Adrianne,
Wilbur Colin,
Housley Gary,
Lipski Janusz,
Funk Greg
Publication year - 2007
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.21.6.a1295-b
Subject(s) - ppads , receptor , p2 receptor , respiratory system , chemistry , electrophysiology , neuroscience , biology , medicine , antagonist , endocrinology , biophysics , biochemistry
Recent data indicate that ATP is released from the ventral respiratory column (VRC) in response to hypoxia where it acts via P2 receptors (Rs) to partially offset hypoxia‐induced reductions in inspiratory frequency (f). This study used rhythmically‐active medullary slices from neonatal rat to: map the VRC to identify the site of maximum ATP sensitivity; identify the P2R subtype(s) mediating the f effects of ATP, and; explore the cellular mechanisms underlying the effects of ATP on f. Microinjections of ATP in the VRC revealed a ‘hotspot’ where ATP evoked a 2.2±0.1 fold increase in f. The hotspot was identified as the PBC based on histology, overlap of labeled injection sites with NK1R immunolabeling and potentiation or inhibition of f at the same site by Substance P or DAMGO respectively. Whole‐cell recording revealed that ATP evoked inward currents in >90% of PBC respiratory neurons, including a P2Y 1 R antagonist‐sensitive current in putative voltage‐dependent pacemaker neurons. Non‐respiratory PBC neurons were also ATP‐sensitive. In summary, the presence of P2Y 1 Rs in the PBC, the relative potency of P2R agonists, and the block of the ATP‐evoked f response and whole‐cell currents in respiratory PBC neurons by MRS2179, suggest that ATP acts via P2Y 1 Rs in the PBC to stimulate rhythm.