{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:23:29Z","timestamp":1789151009933,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA025718"],"award-info":[{"award-number":["AA025718"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Alpha1-containing glycine receptors (GlyRs) are major mediators of synaptic inhibition in the spinal cord and brain stem. Recent studies reported the presence of \u03b12-containing GlyRs in other brain regions, such as nucleus accumbens and cerebral cortex. GlyR activation decreases neuronal excitability associated with sensorial information, motor control, and respiratory functions; all of which are significantly altered during ethanol intoxication. We evaluated the role of \u03b2 GlyR subunits and of two basic amino acid residues, K389 and R390, located in the large intracellular loop (IL) of the \u03b12 GlyR subunit, which are important for binding and functional modulation by G\u03b2\u03b3, the dimer of the trimeric G protein conformation, using HEK-293 transfected cells combined with patch clamp electrophysiology. We demonstrate a new modulatory role of the \u03b2 subunit on ethanol sensitivity of \u03b12 subunits. Specifically, we found a differential allosteric modulation in homomeric \u03b12 GlyRs compared with the \u03b12\u03b2 heteromeric conformation. Indeed, while \u03b12 was insensitive, \u03b12\u03b2 GlyRs were substantially potentiated by ethanol, GTP-\u03b3-S, propofol, Zn<jats:sup>2+<\/jats:sup> and trichloroethanol. Furthermore, a G\u03b2\u03b3 scavenger (ct-GRK2) selectively attenuated the effects of ethanol on recombinant \u03b12\u03b2 GlyRs. Mutations in an \u03b12 GlyR co-expressed with the \u03b2 subunit (\u03b12AA\u03b2) specifically blocked ethanol sensitivity, but not propofol potentiation. These results show a selective mechanism for low ethanol concentration effects on homomeric and heteromeric conformations of \u03b12 GlyRs and provide a new mechanism for ethanol pharmacology, which is relevant to upper brain regions where \u03b12 GlyRs are abundantly expressed.<\/jats:p>","DOI":"10.3389\/fnmol.2021.763868","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T09:42:25Z","timestamp":1637228545000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Modulatory Actions of the Glycine Receptor \u03b2 Subunit on the Positive Allosteric Modulation of Ethanol in \u03b12 Containing Receptors"],"prefix":"10.3389","volume":"14","author":[{"given":"Braulio","family":"Mu\u00f1oz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinidad","family":"Mariqueo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Murath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo E.","family":"Yevenes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Moraga-Cid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Peoples","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis G.","family":"Aguayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1369-1600.2010.00206.x","article-title":"Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens.","volume":"16","author":"Adermark","year":"2011","journal-title":"Addict. 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