{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T22:24:49Z","timestamp":1769379889198,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Key points<\/jats:title><jats:sec><jats:label\/><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>A locally generating, angiotensin\u00a0II (ANG\u00a0II) system is present in the rat carotid body (CB) and up\u2010regulation of this system occurs in certain pathophysiological situations, enhancing sympathetic activity.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Here, we show that, similar to chemoreceptor type I cells, glial\u2010like type\u00a0II cells also express functional AT<jats:sub>1<\/jats:sub>Rs, stimulation of which causes release of Ca<jats:sup>2+<\/jats:sup>from intracellular stores.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>ANG\u00a0II\u2013AT<jats:sub>1<\/jats:sub>R signalling in type\u00a0II cells activates an inward current carried by pannexin\u20101 (Panx\u20101) channels which are known to act as conduits for release of ATP, a key CB excitatory neurotransmitter.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Combined effects of ANG\u00a0II and ATP, which also activates Panx\u20101 currents via P2Y2 receptors, were synergistic; chelating intracellular Ca<jats:sup>2+<\/jats:sup>with BAPTA prevented Panx\u20101 current activation.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We propose that the excitatory function of ANG\u00a0II in the CB involves dual actions at both type I and type II cells.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>A local angiotensin\u2010generating system is present in the carotid body (CB) and increased angiotensin\u00a0II (ANG\u00a0II) signalling contributes to enhanced CB excitation in chronic heart failure (CHF) and after chronic or intermittent hypoxia. ANG\u00a0II actions have thus far been attributed solely to stimulation of AT<jats:sub>1<\/jats:sub>receptors (AT<jats:sub>1<\/jats:sub>Rs) on chemoreceptor type\u00a0I cells. Here, we show that in dissociated rat CB cultures, ANG\u00a0II also stimulates glial\u2010like type\u00a0II cells, identified by P2Y2\u2010receptor\u2010induced intracellular Ca<jats:sup>2+<\/jats:sup>elevation (\u0394[Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). ANG\u00a0II induced a dose\u2010dependent (EC<jats:sub>50<\/jats:sub>\u223c8\u00a0n<jats:sc>m<\/jats:sc>), robust \u0394[Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in type II cells that was reversibly abolished by the AT<jats:sub>1<\/jats:sub>R blocker losartan (1\u00a0\u03bc<jats:sc>m<\/jats:sc>). The ANG\u00a0II\u2010induced \u0394[Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>persisted in Ca<jats:sup>2+<\/jats:sup>\u2010free medium but was sensitive to store depletion with cyclopiazonic acid (1\u00a0\u03bc<jats:sc>m<\/jats:sc>). Similar to P2Y2 receptor agonists, ANG\u00a0II (20\u20131000\u00a0n<jats:sc>m<\/jats:sc>) activated pannexin\u20101 (Panx\u20101) current that was reversibly abolished by carbenoxolone (5\u00a0\u03bc<jats:sc>m<\/jats:sc>). This current arose with a variable delay and was reversibly inhibited by losartan. Repeated application of ANG\u00a0II often led to current run\u2010down, attributable to AT<jats:sub>1<\/jats:sub>R desensitization. When applied to the same cell the combined actions of ANG\u00a0II and ATP on Panx\u20101 current were synergistic. Current induced by either ligand was inhibited by BAPTA\u2010AM (1\u00a0\u03bc<jats:sc>m<\/jats:sc>), suggesting that intracellular Ca<jats:sup>2+<\/jats:sup>signalling contributed to Panx\u20101 channel activation. Because open Panx\u20101 channels release ATP, a key CB excitatory neurotransmitter, it is plausible that paracrine stimulation of type II cells by ANG\u00a0II contributes to enhanced CB excitability, especially in pathophysiological conditions such as CHF and sleep apnoea.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.279299","type":"journal-article","created":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T10:10:46Z","timestamp":1409307046000},"page":"4747-4762","source":"Crossref","is-referenced-by-count":49,"title":["Angiotensin II mobilizes intracellular calcium and activates pannexin\u20101 channels in rat carotid body type II cells via AT<sub>1<\/sub>receptors"],"prefix":"10.1113","volume":"592","author":[{"given":"Sindhubarathi","family":"Murali","sequence":"first","affiliation":[{"name":"Department of Biology McMaster University 1280 Main St West Hamilton Ontario Canada L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biology McMaster University 1280 Main St West Hamilton Ontario Canada L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin A.","family":"Nurse","sequence":"additional","affiliation":[{"name":"Department of Biology McMaster University 1280 Main St West Hamilton Ontario Canada L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.773bj.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0026-895X(25)12929-5","article-title":"Angiotensin II receptor subtypes and biological responses in the adrenal cortex and medulla","volume":"40","author":"Balla T","year":"1991","journal-title":"Mol Pharmacol"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00048.2005"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-012-9862-y"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110036"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.081"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0031-6997(24)01458-3","article-title":"International Union of Pharmacology. 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