{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:55:40Z","timestamp":1781585740628,"version":"3.54.5"},"reference-count":11,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["IF\\R1\\251048"],"award-info":[{"award-number":["IF\\R1\\251048"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    NS5806 is a diaryl\u2010urea small molecule developed for the treatment of pain and neurological disorders. A potent activator of K\n                    <jats:sub>v<\/jats:sub>\n                    4.3 potassium channels, it is widely used to study K\n                    <jats:sub>v<\/jats:sub>\n                    4 channel physiology in excitable cells, including trigeminal neurons. Surprisingly, we found that NS5806 produced a significant, robust hyperpolarization of the resting membrane potential of all trigeminal neurons tested. Given the structural similarity of NS5806 to other negatively charged activator compounds with broad potassium channel activity, we investigated whether NS5806 might also modulate the two\u2010pore domain potassium (K2P) TREK channels, which are abundantly expressed in sensory neurons. Here we show that NS5806 activates both TREK\u20101 and TREK\u20102 channels. While NS5806 is described as a K\n                    <jats:sub>v<\/jats:sub>\n                    4\u2010selective activator, our data suggest that its effects on trigeminal and other neurons may arise from concurrent activation of multiple potassium channel types, including TREK\u20101 and TREK\u20102.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70264","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:01:13Z","timestamp":1778821273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of\n                    <scp>TREK<\/scp>\n                    \u20101 and\n                    <scp>TREK<\/scp>\n                    \u20102 Two\u2010Pore Domain Potassium Channels by the K\n                    <sub>v<\/sub>\n                    4 Channel Modulator,\n                    <scp>NS5806<\/scp>"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6778-9929","authenticated-orcid":false,"given":"E. L.","family":"Veale","sequence":"first","affiliation":[{"name":"Medway School of Pharmacy University of Kent and University of Greenwich  Chatham Maritime UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-5952","authenticated-orcid":false,"given":"P. M.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Metrion Biosciences  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-6142","authenticated-orcid":false,"given":"A. M.","family":"Rush","sequence":"additional","affiliation":[{"name":"Metrion Biosciences  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8308-7938","authenticated-orcid":false,"given":"E. B.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Metrion Biosciences  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6094-2890","authenticated-orcid":false,"given":"A.","family":"Mathie","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy University of Kent and University of Greenwich  Chatham Maritime UK"},{"name":"School of Life Sciences University of Westminster  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031419"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.577528"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2010.00859"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902010RR"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.08.017"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2036\u201020.2021"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.229013"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2016.038"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2012.01.002"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav0569"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.4c01012"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70264","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.70264","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:21:36Z","timestamp":1781583696000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.70264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":11,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/prp2.70264"],"URL":"https:\/\/doi.org\/10.1002\/prp2.70264","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"2026-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70264"}}