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In darkness or in green light,\n                      <jats:italic>trans\u2010<\/jats:italic>\n                      QAQ blocks voltage\u2010gated K\n                      <jats:sup>+<\/jats:sup>\n                      and Na\n                      <jats:sup>+<\/jats:sup>\n                      channels and silences action potentials in pain\u2010sensing neurons. Upon photo\u2010isomerization to\n                      <jats:italic>cis<\/jats:italic>\n                      with near UV light, QAQ blockade is rapidly relieved, restoring neuronal activity. However, the molecular mechanism of\n                      <jats:italic>cis<\/jats:italic>\n                      and\n                      <jats:italic>trans<\/jats:italic>\n                      QAQ blockade is not known. Moreover, the absorption spectrum of QAQ requires UV light for photo\u2010control, precluding use deep inside neural tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Electrophysiology and molecular modelling were used to characterize the binding of\n                      <jats:italic>cis<\/jats:italic>\n                      and\n                      <jats:italic>trans<\/jats:italic>\n                      QAQ to voltage\u2010gated K\n                      <jats:sup>+<\/jats:sup>\n                      channels and to develop quaternary ammonium\u2013ethylamine\u2013azobenzene\u2013quaternary ammonium (QENAQ), a red\u2010shifted QAQ derivative controlled with visible light.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>trans<\/jats:italic>\n                      QAQ was sixfold more potent than\n                      <jats:italic>cis<\/jats:italic>\n                      QAQ, in blocking current through Shaker K\n                      <jats:sup>+<\/jats:sup>\n                      channels. Both isomers were use\u2010dependent, open channel blockers, binding from the cytoplasmic side, but only\n                      <jats:italic>trans<\/jats:italic>\n                      QAQ block was slightly voltage dependent. QENAQ also blocked native K\n                      <jats:sup>+<\/jats:sup>\n                      and Na\n                      <jats:sup>+<\/jats:sup>\n                      channels preferentially in the\n                      <jats:italic>trans<\/jats:italic>\n                      state. QENAQ was photo\u2010isomerized to\n                      <jats:italic>cis<\/jats:italic>\n                      with blue light and spontaneously reverted to\n                      <jats:italic>trans<\/jats:italic>\n                      within seconds in darkness, enabling rapid photo\u2010control of action potentials in sensory neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Light\u2010switchable local anaesthetics provide a means to non\u2010invasively photo\u2010control pain signalling with high selectivity and fast kinetics. Understanding the mode of action of QAQ and related compounds will help to design of drugs with improved photo\u2010pharmacological properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Linked Articles<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.12\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.12\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.13923","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T23:42:36Z","timestamp":1498002156000},"page":"2296-2311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Understanding and improving photo\u2010control of ion channels in nociceptors with azobenzene photo\u2010switches"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8839-7481","authenticated-orcid":false,"given":"Alexandre","family":"Mourot","sequence":"first","affiliation":[{"name":"Sorbonne 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