{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:14:08Z","timestamp":1781010848956,"version":"3.54.1"},"reference-count":63,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Effective optogenetic inhibition of neuronal activity requires tools that reliably silence neurons across cell types and conditions. K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010selective channelrhodopsins (KCRs) have emerged as attractive alternatives to chloride\u2010conducting channels for optogenetic inhibition of cellular excitability, but many KCR variants exhibit an ion selectivity shift toward Na\n                    <jats:sup>+<\/jats:sup>\n                    under prolonged illumination. Through behavioral and electrophysiological analyses in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , and\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , it is found that both the absolute K\n                    <jats:sup>+<\/jats:sup>\n                    to Na\n                    <jats:sup>+<\/jats:sup>\n                    permeability ratio and its stability over time determine the inhibition to activation transition, which limits their utility for silencing neural circuits. Among tested variants, the KCR1\u2010C29D mutant shows a relatively high and the most stable K\n                    <jats:sup>+<\/jats:sup>\n                    to Na\n                    <jats:sup>+<\/jats:sup>\n                    permeability ratio during illumination. While other KCR variants often evoke excitatory responses, KCR1\u2010C29D consistently provides robust in vivo inhibition across cell types, illumination conditions, and species. This work addresses a key limitation of KCR optogenetics and establishes KCR1\u2010C29D as a superior and reliable inhibitory tool. These findings highlight the stability of ion selectivity as a design criterion and provide guidance for the design of next generation optogenetic tools.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509180","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:55:44Z","timestamp":1762754144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stabilized Ion Selectivity Corrects Activation Drift in Kalium Channelrhodopsins"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiao","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Neurophysiology Institute of Physiology University Wuerzburg  97070 Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Institute of Physiology University Wuerzburg  97070 Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Ott","sequence":"additional","affiliation":[{"name":"Program in Neuroscience and Behavioral Disorders Duke\u2010NUS Medical School  169857 Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Program in Neuroscience and Behavioral Disorders Duke\u2010NUS Medical School  169857 Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Ruse","sequence":"additional","affiliation":[{"name":"Buchmann Institute of Molecular Life Sciences Goethe University  60438 Frankfurt Germany"},{"name":"Institute of Biophysical Chemistry Department of Molecular Sciences Goethe University  60438 Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Dannh\u00e4user","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Institute of Physiology University Wuerzburg  97070 Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jacobi","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Institute of Physiology University Wuerzburg  97070 Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Ehmann","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology Institute of Biology Leipzig University  04103 Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Sachidanandan","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology Institute of Biology Leipzig University  04103 Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Nagel","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Institute of Physiology University Wuerzburg  97070 Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Heckmann","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Institute of Physiology University Wuerzburg  97070 Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Kittel","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology Institute of Biology Leipzig University  04103 Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Gottschalk","sequence":"additional","affiliation":[{"name":"Buchmann Institute of Molecular Life Sciences Goethe University  60438 Frankfurt Germany"},{"name":"Institute of Biophysical Chemistry Department of Molecular Sciences Goethe University  60438 Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Claridge\u2010Chang","sequence":"additional","affiliation":[{"name":"Program in Neuroscience and Behavioral Disorders Duke\u2010NUS Medical School  169857 Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-9443","authenticated-orcid":false,"given":"Shiqiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Institute of Physiology University Wuerzburg  97070 Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583523000033"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-arplant-071122-094840"},{"key":"e_1_2_9_3_1","first-page":"1555","volume":"88","author":"Govorunova E. 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