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Herein, we set out to determine the effect of H<jats:sub>2<\/jats:sub>S on <jats:italic>\u03b1<\/jats:italic>\u2010amino\u20103\u2010hydroxy\u20105\u2010methylisoxazole\u20104\u2010propionic acid receptor (<jats:styled-content style=\"fixed-case\">AMPAR<\/jats:styled-content>) and its mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">BS<\/jats:styled-content><jats:sup>3<\/jats:sup> protein cross\u2010linking, Western blot, patch clamp, and biotin\u2010switch assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bath application of H<jats:sub>2<\/jats:sub>S donor Na<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> (50 and 100 <jats:italic>\u03bc<\/jats:italic>M) rapidly promoted surface insertion of hippocampal <jats:styled-content style=\"fixed-case\">AMPAR<\/jats:styled-content> GluR1 subunit. This effect can be abolished by dithiothreitol (<jats:styled-content style=\"fixed-case\">DTT<\/jats:styled-content>) and mimicked by Na<jats:sub>2<\/jats:sub>S<jats:sub>4<\/jats:sub>, indicating that a sulfhydration\u2010dependent mechanism may be involved. Na<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> increased <jats:styled-content style=\"fixed-case\">APMAR<\/jats:styled-content>\u2010mediated <jats:styled-content style=\"fixed-case\">EPSC<\/jats:styled-content> and led to an elevation of GluR2\u2010lacking <jats:styled-content style=\"fixed-case\">AMPAR<\/jats:styled-content> content. Notably, Na<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> did not increase the sulfhydration of <jats:styled-content style=\"fixed-case\">AMPAR<\/jats:styled-content> subunits, but it significantly increased the phosphorylation of GluR1 at serine\u2010831 and serine\u2010845 sites. Postsynaptic signal pathways that control GluR1 phosphorylation, such as protein kinase A (<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>), protein kinase C, and calcium\/calmodulin\u2010dependent protein kinases <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content>), were sulfhydrated, activated by Na<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>, and these effects can be occluded by <jats:styled-content style=\"fixed-case\">DTT<\/jats:styled-content>. H<jats:sub>2<\/jats:sub>S increased S\u2010sulfhydration of protein phosphatase type 2A (<jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>2A), which may be partially involved in the activation of signal pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that H<jats:sub>2<\/jats:sub>S promotes surface insertion of <jats:styled-content style=\"fixed-case\">AMPAR<\/jats:styled-content>s via phosphorylation of GluR1, which depends on a sulfhydration\u2010mediated mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12585","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T06:16:43Z","timestamp":1467785803000},"page":"789-798","source":"Crossref","is-referenced-by-count":25,"title":["Hydrogen Sulfide Promotes Surface Insertion of Hippocampal <scp>AMPA<\/scp> Receptor GluR1 Subunit via Phosphorylating at Serine\u2010831\/Serine\u2010845 Sites Through a Sulfhydration\u2010Dependent Mechanism"],"prefix":"10.1111","volume":"22","author":[{"given":"Yuan\u2010Long","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Hong","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"Key Laboratory of Neurological Diseases (HUST) Ministry of Education of China Wuhan Hubei China"},{"name":"The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province Wuhan Hubei China"},{"name":"Laboratory of Neuropsychiatric Diseases The Institute of Brain Research Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang\u2010Li","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of 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