{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:17:57Z","timestamp":1769386677952,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T00:00:00Z","timestamp":1493078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 142469"],"award-info":[{"award-number":["MOP 142469"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>5\u2010HT is a neuromodulator released from carotid body (CB) chemoreceptor (type I) cells and facilitates the sensory discharge following chronic intermittent hypoxia (CIH).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the present study, we show that, in addition to type I cells, adjacent glial\u2010like type II cells express functional, ketanserin\u2010sensitive 5\u2010HT<jats:sub>2<\/jats:sub> receptors, and their stimulation increases cytoplasmic Ca<jats:sup>2+<\/jats:sup> derived from intracellular stores.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In type II cells, 5\u2010HT activated a ketanserin\u2010sensitive inward current (<jats:italic>I<\/jats:italic><jats:sub>5\u2010HT<\/jats:sub>) that was similar to that (<jats:italic>I<\/jats:italic><jats:sub>UTP<\/jats:sub>) activated by the P2Y2R agonist, UTP.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>As previously shown for <jats:italic>I<\/jats:italic><jats:sub>UTP<\/jats:sub>, <jats:italic>I<\/jats:italic><jats:sub>5\u2010HT<\/jats:sub> was inhibited by BAPTA\u2010AM and carbenoxolone (5\u00a0\u03bc<jats:sc>m<\/jats:sc>), a putative blocker of ATP\u2010permeable pannexin (Panx)\u20101 channels; <jats:italic>I<\/jats:italic><jats:sub>UTP<\/jats:sub> was reversibly inhibited by the specific Panx\u20101 mimetic peptide channel blocker, <jats:sup>10<\/jats:sup>Panx peptide.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Paracrine stimulation of type II cells by 5\u2010HT, leading to ATP release via Panx\u20101 channels, may contribute to CB excitability, especially in pathophysiological conditions associated with CIH (e.g. obstructive sleep apnoea).<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5\u2010HT and increased autocrine\u2013paracrine 5\u2010HT<jats:sub>2<\/jats:sub> receptor signalling contributes to sensory long\u2010term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial\u2010like type II cells can respond to CB paracrine signals by elevating intracellular calcium (\u0394[Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) and activating carbenoxolone\u2010sensitive, ATP\u2010permeable, pannexin (Panx)\u20101\u2010like channels. In the present study, using dissociated rat CB cultures, we found that 5\u2010HT induced \u0394[Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> responses in a subpopulation of type I cells, as well as in most (\u223c67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP. The 5\u2010HT\u2010induced Ca<jats:sup>2+<\/jats:sup> response in type II cells was dose\u2010dependent (EC<jats:sub>50<\/jats:sub> \u223c183\u00a0n<jats:sc>m<\/jats:sc>) and largely inhibited by the 5\u2010HT<jats:sub>2A<\/jats:sub> receptor blocker, ketanserin (1\u00a0\u03bc<jats:sc>m<\/jats:sc>), and also arose mainly from intracellular stores. 5\u2010HT also activated an inward current (<jats:italic>I<\/jats:italic><jats:sub>5\u2010HT<\/jats:sub>) in type II cells (EC<jats:sub>50<\/jats:sub> \u223c200\u00a0n<jats:sc>m<\/jats:sc>) that was reversibly inhibited by ketanserin (1\u201310\u00a0n<jats:sc>m<\/jats:sc>), the Ca<jats:sup>2+<\/jats:sup> chelator BAPTA\u2010AM (5\u00a0\u03bc<jats:sc>m<\/jats:sc>), and low concentrations of carbenoxolone (5\u00a0\u03bc<jats:sc>m<\/jats:sc>), a putative Panx\u20101 channel blocker. <jats:italic>I<\/jats:italic><jats:sub>5\u2010HT<\/jats:sub> reversed direction at approximately \u221211\u00a0mV and was indistinguishable from the UTP\u2010activated current (<jats:italic>I<\/jats:italic><jats:sub>UTP<\/jats:sub>). Consistent with a role for Panx\u20101 channels, <jats:italic>I<\/jats:italic><jats:sub>UTP<\/jats:sub> was reversibly inhibited by the specific Panx\u20101 mimetic peptide blocker <jats:sup>10<\/jats:sup>Panx (100\u00a0\u03bc<jats:sc>m<\/jats:sc>), although not by its scrambled control peptide (<jats:sup>sc<\/jats:sup>Panx). Because ATP is an excitatory CB neurotransmitter, it is possible that the contribution of enhanced 5\u2010HT signalling to the increased sensory discharge during CIH may occur, in part, by a boosting of ATP release from type II cells via Panx\u20101 channels.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273473","type":"journal-article","created":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T21:12:30Z","timestamp":1490303550000},"page":"4261-4277","source":"Crossref","is-referenced-by-count":21,"title":["Evidence that 5\u2010HT stimulates intracellular Ca<sup>2+<\/sup> signalling and activates pannexin\u20101 currents in type II cells of the rat carotid body"],"prefix":"10.1113","volume":"595","author":[{"given":"Sindhubarathi","family":"Murali","sequence":"first","affiliation":[{"name":"Department of Biology McMaster University  Hamilton Ontario 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