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To selectively enhance G\n                    <jats:sub>i\/o<\/jats:sub>\n                    -mediated GIRK currents, we created expression cassettes that coupled the activity of a GIRK subunit to the light-activated G\n                    <jats:sub>i\/o<\/jats:sub>\n                    -coupled GPCRs Opn4L (an opsin also known as melanopsin), longwave-sensitive opsin Opn1, parapinopsin, or Opn7b. We used the GIRK1 F137S mutant because of its fast activation, generation of large currents, and formation of homomeric channels, which reduced the size of the expression cassette. We demonstrated that light-mediated activation of GIRK1\n                    <jats:sup>F137S<\/jats:sup>\n                    through the opsins induced robust GIRK currents in HEK293 cells, cardiomyocytes, and cerebellar Purkinje neurons. Moreover, coupling GIRK1\n                    <jats:sup>F137S<\/jats:sup>\n                    activation to the promiscuous Opn4L changed the net effect of G protein signaling from G\n                    <jats:sub>q\/11<\/jats:sub>\n                    -mediated excitation to G\n                    <jats:sub>i\/o<\/jats:sub>\n                    -mediated inhibition in cerebellar Purkinje neurons and cardiomyocytes. Thus, our tools optimize the use of GIRK activity in the optogenetic control of the G\n                    <jats:sub>i\/o<\/jats:sub>\n                    pathway in excitable cells.\n                  <\/jats:p>","DOI":"10.1126\/scisignal.adw4374","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:58:22Z","timestamp":1792519102000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Improving optogenetic control over G\n                    <sub>i\/o<\/sub>\n                    -coupled receptor signaling by optimized GIRK channel expression"],"prefix":"10.1126","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7233-8679","authenticated-orcid":true,"given":"Brix","family":"M\u00fccher","sequence":"first","affiliation":[{"name":"Department of Zoology and Neurobiology, Ruhr University Bochum, 44801 Bochum, 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