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The discovery of agonistic\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>Ks<\/jats:italic>\n                    <\/jats:sub>\n                    modulators may offer a new potential strategy in pharmacological treatment of this disorder. The benzodiazepine derivative (\n                    <jats:italic>R<\/jats:italic>\n                    )-L3 potently activates K\n                    <jats:sub>v<\/jats:sub>\n                    7.1 channels and shortens action potential duration, thus may represent a starting point for drug development. However, the molecular mechanisms underlying modulation by (\n                    <jats:italic>R<\/jats:italic>\n                    )-L3 are still unknown. By combining alanine scanning mutagenesis, non-canonical amino acid incorporation, voltage-clamp electrophysiology and fluorometry, and\n                    <jats:italic>in silico<\/jats:italic>\n                    protein modelling, we show that (\n                    <jats:italic>R<\/jats:italic>\n                    )-L3 not only stimulates currents by allosteric modulation of the pore domain but also alters the kinetics independently from the pore domain effects. We identify novel (\n                    <jats:italic>R<\/jats:italic>\n                    )-L3-interacting key residues in the lower S4-segment of K\n                    <jats:sub>v<\/jats:sub>\n                    7.1 and observed an uncoupling of the outer S4 segment with the inner S5, S6 and selectivity filter segments.\n                  <\/jats:p>","DOI":"10.1038\/s42003-022-03229-8","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T06:21:23Z","timestamp":1648794083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A benzodiazepine activator locks Kv7.1 channels open by electro-mechanical uncoupling"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3847-7539","authenticated-orcid":false,"given":"Julian A.","family":"Schreiber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"M\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Zaydman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Beller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Ritter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Wrobel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Strutz-Seebohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9433-687X","authenticated-orcid":false,"given":"Niels","family":"Decher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9482-9749","authenticated-orcid":false,"given":"Nicole","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"D\u00fcfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-8417","authenticated-orcid":false,"given":"Bernhard","family":"W\u00fcnsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9198-6332","authenticated-orcid":false,"given":"Jianmin","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-5373","authenticated-orcid":false,"given":"Guiscard","family":"Seebohm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"3229_CR1","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1152\/physiol.00031.2005","volume":"20","author":"T Jespersen","year":"2005","unstructured":"Jespersen, T., Grunnet, M. & Olesen, S. 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