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ATP released in the ventrolateral medulla oblongata during hypoxia attenuates the secondary depression. We explored a working hypothesis that vesicular release of ATP by astrocytes in the pre\u2010B\u00f6tzinger Complex (preB\u00f6tC) inspiratory rhythm\u2010generating network acts via P2Y\n 1<\/jats:sub>\n receptors to mediate this effect. Blockade of vesicular exocytosis in preB\u00f6tC astrocytes bilaterally (using an adenoviral vector to specifically express tetanus toxin light chain in astrocytes) reduced the HVR in anaesthetized rats, indicating that exocytotic release of a gliotransmitter within the preB\u00f6tC contributes to the hypoxia\u2010induced increases in ventilation. Unilateral blockade of P2Y\n 1<\/jats:sub>\n receptors in the preB\u00f6tC via local antagonist injection enhanced the secondary respiratory depression, suggesting that a significant component of the phase II increase in ventilation is mediated by ATP acting at P2Y\n 1<\/jats:sub>\n receptors.\n In vitro<\/jats:italic>\n responses of the preB\u00f6tC inspiratory network, preB\u00f6tC inspiratory neurons and cultured preB\u00f6tC glia to purinergic agents demonstrated that the P2Y\n 1<\/jats:sub>\n receptor\u2010mediated increase in fictive inspiratory frequency involves Ca\n 2+<\/jats:sup>\n recruitment from intracellular stores leading to increases in intracellular Ca\n 2+<\/jats:sup>\n ([Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n ) in inspiratory neurons and glia. These data suggest that ATP is released by preB\u00f6tC astrocytes during hypoxia and acts via P2Y\n 1<\/jats:sub>\n receptors on inspiratory neurons (and\/or glia) to evoke Ca\n 2+<\/jats:sup>\n release from intracellular stores and an increase in ventilation that counteracts the hypoxic respiratory depression.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp274727","type":"journal-article","created":{"date-parts":[[2017,7,5]],"date-time":"2017-07-05T09:52:55Z","timestamp":1499248375000},"page":"3245-3269","source":"Crossref","is-referenced-by-count":99,"title":["Release of ATP by pre\u2010B\u00f6tzinger complex astrocytes contributes to the hypoxic ventilatory response via a Ca\n 2+<\/sup>\n \u2010dependent P2Y\n 1<\/sub>\n receptor mechanism"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3682-7208","authenticated-orcid":false,"given":"Vishaal","family":"Rajani","sequence":"first","affiliation":[{"name":"Department of Physiology, Neuroscience 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