{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T12:36:55Z","timestamp":1754483815081},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31271164","31471064","31421091","81420108015","31571103","81570081","31530035"],"award-info":[{"award-number":["31271164","31471064","31421091","81420108015","31571103","81570081","31530035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (<jats:styled-content style=\"fixed-case\">GG<\/jats:styled-content>) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (<jats:styled-content style=\"fixed-case\">HMN<\/jats:styled-content>s) and the underlying signaling mechanisms have remained elusive. Here, whole\u2010cell patch\u2010clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited <jats:styled-content style=\"fixed-case\">HMN<\/jats:styled-content>s with an inward current under voltage\u2010clamp and a depolarization membrane potential under current\u2010clamp via histamine H<jats:sub>1<\/jats:sub> receptors (H<jats:sub>1<\/jats:sub>Rs). The phospholipase C inhibitor U\u201073122 blocked H<jats:sub>1<\/jats:sub>Rs\u2010mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on <jats:styled-content style=\"fixed-case\">HMN<\/jats:styled-content>s were H<jats:sub>1<\/jats:sub>R\/G<jats:sub>q\/11<\/jats:sub>\/phospholipase C\/inositol\u20101,4,5\u2010trisphosphate (<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content><jats:sub>3<\/jats:sub>). The effects of histamine were also dependent on extracellular Na<jats:sup>+<\/jats:sup> and intracellular Ca<jats:sup>2+<\/jats:sup>, which took place via activation of Na<jats:sup>+<\/jats:sup>\u2010Ca<jats:sup>2+<\/jats:sup> exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on <jats:styled-content style=\"fixed-case\">HMN<\/jats:styled-content>s. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea.<\/jats:p><\/jats:sec><jats:sec><jats:label \/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13548-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nWe proposed the post\u2010synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H<jats:sub>1<\/jats:sub>Rs via PLC and IP<jats:sub>3<\/jats:sub>, increases Ca<jats:sup>2+<\/jats:sup> releases from intracellular stores, promotes Na<jats:sup>+<\/jats:sup> influx and Ca<jats:sup>2+<\/jats:sup> efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13548","type":"journal-article","created":{"date-parts":[[2016,1,26]],"date-time":"2016-01-26T11:37:37Z","timestamp":1453808257000},"page":"277-286","source":"Crossref","is-referenced-by-count":10,"title":["Signaling mechanism underlying the histamine\u2010modulated action of hypoglossal motoneurons"],"prefix":"10.1111","volume":"137","author":[{"given":"Zi\u2010Long","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine Center of Snoring and Sleep Apnea Medicine Zhongshan Hospital of Fudan University Shanghai China"},{"name":"State Key Laboratory of Medical Neurobiology, and Shanghai Key Laboratory of Bioactive Small Molecules Department of Pharmacology School of Basic Medical Sciences Fudan University Shanghai China"},{"name":"The Institutes of Brain Science and 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