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Small molecules that restore K\n                      <jats:sub>v<\/jats:sub>\n                      1.1 activity hold promise as targeted therapies for EA1, yet current pharmacological strategies remain limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Two electrode voltage\u2010clamp electrophysiology and the\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Xenopus laevis<\/jats:italic>\n                      <\/jats:styled-content>\n                      oocyte expression system were used to study effects of carnosic acid, a phenolic diterpene from\n                      <jats:italic>Salvia rosmarinus<\/jats:italic>\n                      (rosemary) leaf extract on K\n                      <jats:sub>v<\/jats:sub>\n                      1.1\u2010linked EA1 mutant channels. We assessed ataxia therapeutic efficacy by comparing performance of\n                      <jats:italic>Kcna1<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      and\n                      <jats:italic>Kcna1<\/jats:italic>\n                      <jats:sup>E283K\/+<\/jats:sup>\n                      mice, a model of human EA1, on a balance beam under isoproterenol challenge in the absence or presence of 0.3\u2010mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      carnosic acid.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Rosemary leaf extract and rosemary metabolite carnosic acid are efficacious K\n                      <jats:sub>v<\/jats:sub>\n                      1.1 openers. Carnosic acid fully or partially corrects heterozygous, heteromeric K\n                      <jats:sub>v<\/jats:sub>\n                      1.1 EA1 mutant channel activity\n                      <jats:italic>in vitro<\/jats:italic>\n                      and restores normal function in K\n                      <jats:sub>v<\/jats:sub>\n                      1.1\n                      <jats:sup>E283K\/+<\/jats:sup>\n                      mice at 0.3\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      . Experimental validation of unbiased in silico docking reveals carnosic acid occupies a binding pocket between the S1 and S4 helices of the voltage\u2010sensing domain (VSD) of K\n                      <jats:sub>v<\/jats:sub>\n                      1.1. Finally, we determined the chemical properties that endow carnosic acid with the ability to open K\n                      <jats:sub>v<\/jats:sub>\n                      1.1 channels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      Our findings uncover a K\n                      <jats:sub>v<\/jats:sub>\n                      1.1 opener with the potential to reverse EA1 and other K\n                      <jats:sub>v<\/jats:sub>\n                      1.1\u2010linked disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70578","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:32:03Z","timestamp":1784946723000},"page":"6179-6198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rosemary metabolite carnosic acid opens K\n                    <sub>v<\/sub>\n                    1.1 via its voltage sensor and corrects K\n                    <sub>v<\/sub>\n                    1.1\u2010linked episodic ataxia in mice"],"prefix":"10.1111","volume":"183","author":[{"given":"R\u00edan W.","family":"Manville","sequence":"first","affiliation":[{"name":"Bioelectricity Laboratory, Dept. of Physiology and Biophysics, School of Medicine University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan F.","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory, Dept. of Physiology and Biophysics, School of Medicine University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanh A.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory, Dept. of Physiology and Biophysics, School of Medicine University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Departments of Physiology &amp; Biophysics, Pediatrics, and Pharmaceutical Sciences, Susan and Henry Samueli College of Health Sciences University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derk J.","family":"Hogenkamp","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory, Dept. of Physiology and Biophysics, School of Medicine University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve A. 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