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GPN neurons give rise to the \u201cefferent inhibitory\u201d pathway via a plexus of neuronal nitric oxide (NO) synthase-positive fibers, believed to be responsible for CB chemoreceptor inhibition via NO release. Although NO is elevated during natural CB stimulation by hypoxia, the underlying mechanisms are unclear. We hypothesized that ATP, released by rat CB chemoreceptors (type 1 cells) and\/or red blood cells during hypoxia, may directly activate GPN neurons and contribute to NO-mediated inhibition. Using combined electrophysiological, molecular, and confocal immunofluorescence techniques, we detected the expression of multiple P2X receptors in GPN neurons. These receptors involve at least four different purinergic subunits: P2X<jats:sub>2<\/jats:sub>[and the splice variant P2X<jats:sub>2(b)<\/jats:sub>], P2X<jats:sub>3<\/jats:sub>, P2X<jats:sub>4<\/jats:sub>, and P2X<jats:sub>7<\/jats:sub>. Using a novel coculture preparation of CB type I cell clusters and GPN neurons, we tested the role of P2X signaling on CB function. In cocultures, fast application of ATP, or its synthetic analog 2\u2032,3\u2032-<jats:italic>O<\/jats:italic>-(4 benzoylbenzoyl)-ATP, caused type I cell hyperpolarization that was prevented in the presence of the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide potassium. These data suggest that ATP released during hypoxic stress from CB chemoreceptors (and\/or red blood cells) will cause GPN neuron depolarization mediated by multiple P2X receptors. Activation of this pathway will lead to calcium influx and efferent inhibition of CB chemoreceptors via NO synthesis and consequent release.<\/jats:p>","DOI":"10.1523\/jneurosci.1672-06.2006","type":"journal-article","created":{"date-parts":[[2006,9,13]],"date-time":"2006-09-13T16:59:40Z","timestamp":1158166780000},"page":"9482-9493","source":"Crossref","is-referenced-by-count":51,"title":["Expression of Multiple P2X Receptors by Glossopharyngeal Neurons Projecting to Rat Carotid Body O<sub>2<\/sub>-Chemoreceptors: Role in Nitric Oxide-Mediated Efferent Inhibition"],"prefix":"10.1523","volume":"26","author":[{"given":"Ver\u00f3nica 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