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Benzodiazepines bind\n                    <jats:styled-content style=\"fixed-case\">\n                      GABA\n                      <jats:sub>A<\/jats:sub>\n                    <\/jats:styled-content>\n                    receptors at the extracellular interface of the \u03b1 and \u03b3 subunits. Within the \u03b1 subunit, the benzodiazepine binding site is defined by three highly conserved structural loops, loops A\u2010C. Although previous mutagenesis studies have identified His102 in Loop A as important for benzodiazepine modulation of\n                    <jats:styled-content style=\"fixed-case\">\n                      GABA\n                      <jats:sub>A<\/jats:sub>\n                    <\/jats:styled-content>\n                    receptors, the functional roles of many of the other conserved residues in loops A\u2010C remain incompletely understood. In this study, we made single mutations in loops A\u2010C of the benzodiazepine binding\u2010site across all six \u03b1 subunits. We used whole\u2010cell patch clamp recording to measure the functional effects of these mutations on midazolam potentiation. The results showed that mutating the threonine in loop B and serine in loop C (Thr163 and S206 in human \u03b11) did not abolish the receptors\u2019 responsiveness to midazolam, as the \u03b11(H102R) mutation did. The loop C mutations exhibited a novel array of \u03b1\u2010isoform specific effects on midazolam potentiation. The \u03b13(S230I) and \u03b15(S209I) mutations had the largest effect on midazolam potentiation, increasing the efficacy of midazolam. Novel benzodiazepines targeting loop C may represent a future direction for designing new drugs that specifically alter the activity of \u03b13\u2010 and \u03b15\u2010containing\n                    <jats:styled-content style=\"fixed-case\">\n                      GABA\n                      <jats:sub>A<\/jats:sub>\n                    <\/jats:styled-content>\n                    receptors.\n                  <\/jats:p>","DOI":"10.1002\/prp2.433","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:31:56Z","timestamp":1542155516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The role of loops B and C in determining the potentiation of\n                    <scp>\n                      GABA\n                      <sub>A<\/sub>\n                    <\/scp>\n                    receptors by midazolam"],"prefix":"10.1002","volume":"6","author":[{"given":"Olivia 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