{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:48:54Z","timestamp":1785743334315,"version":"3.56.0"},"reference-count":94,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["19\/687"],"award-info":[{"award-number":["19\/687"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Cardiorespiratory homeostasis is maintained by carotid body (CB) peripheral chemoreceptors that monitor blood oxygen and stimulate breathing. While proportionality between peripheral chemoreflex sensitivity and respiratory response is relative to hypoxia severity, the fundamental regulatory mechanisms remain unknown. We hypothesized that intercellular amino acid transmission between glomus cells modulates CB sensitivity. We identified a full complement of glutamate and gamma\u2010aminobutyric acid (GABA) synaptic signalling machinery in the CB. During hypoxia stimulation, glutamate acting via NMDA receptors (NMDA\u2010R) stimulated CB afferents while releasing GABA, which acted on GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors to rapidly attenuate afferent drive mediated by purinergic P2X receptors. We propose that this intrinsic \u2018accelerator\u2013brake\u2019 mechanism regulates CB sensitivity to hypoxia. Further, glutamate and NMDA\u2010R were essential for long\u2010term facilitation (LTF) of respiratory chemoreflex responses induced by repeated hypoxia or glutamate exposures. The accelerator\u2013brake mechanism establishes the set\u2010point of chemoreflex gain and provides plasticity for modulation, explaining ventilatory LTF to repeated bouts of hypoxia.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70591-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>An intra\u2010carotid body interaction between glutamate and GABA transmission is crucial for the generation of the biphasic carotid body afferent nerve response when stimulated with low doses of sodium cyanide.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Glutamate stimulates the carotid body chemoreflex to increase inspiratory drive without affecting sympathetic activity, heart rate or perfusion pressure, indicating selective activation of a carotid body respiratory reflex arc.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Repetitive application of glutamate to the carotid body sensitizes chemoreflex phrenic nerve responses producing long\u2010term facilitation.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp289334","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T16:35:31Z","timestamp":1778862931000},"page":"6196-6224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amino acid modulation of the carotid body selectively modulates peripheral chemoreceptor respiratory reflex"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3281-2772","authenticated-orcid":false,"given":"Olivia M. 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