{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:54:46Z","timestamp":1790178886969,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Orsz\u00e1gos Tudom\u00e1nyos Kutat\u00e1si Alapprogramok","doi-asserted-by":"publisher","award":["K108496"],"award-info":[{"award-number":["K108496"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Cloxyquin (5\u2010cloroquinolin\u20108\u2010ol) has been described as an activator of TRESK (K<jats:sub>2P<\/jats:sub>18.1, TWIK\u2010related spinal cord K<jats:sup>+<\/jats:sup> channel) background potassium channel. We have examined the specificity of the drug by testing several K<jats:sub>2P<\/jats:sub> channels. We have investigated the mechanism of cloxyquin\u2010mediated TRESK activation, focusing on the differences between the physiologically relevant regulatory states of the channel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Potassium currents were measured by two\u2010electrode voltage clamp in <jats:italic>Xenopus<\/jats:italic> oocytes and by whole\u2010cell patch clamp in mouse dorsal root ganglion (DRG) neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Cloxyquin (100 \u00b5M) activated mouse and human TRESK 4.4 \u00b1 0.3 (<jats:italic>n<\/jats:italic> = 28) and 3.9 \u00b1 0.3\u2010fold (<jats:italic>n<\/jats:italic> = 8), respectively. The drug selectively targeted TRESK in the K<jats:sub>2P<\/jats:sub> channel family and exerted state\u2010dependent effects. TRESK was potently activated by cloxyquin in the resting state. However, after robust activation of the current by the calcium signal, evoked by stimulation of Gq\u2010coupled receptors, the compound did not influence mouse TRESK and only slightly affected the human channel. The constitutively active mutant channels, mimicking the dephosphorylated state (S276A) or containing altered channel pore (F156A and F364A), were not further stimulated by cloxyquin. In a subpopulation of isolated DRG neurons, cloxyquin substantially activated the background potassium current.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Cloxyquin activates TRESK by a Ca<jats:sup>2+<\/jats:sup>\/calcineurin\u2010independent mechanism. The drug is specific for TRESK within the K<jats:sub>2P<\/jats:sub> channel family and useful for studying TRESK currents in native cells. The state\u2010dependent pharmacological profile of this channel should be considered in the development of therapeutics for migraine and other nociceptive disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13821","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T15:46:48Z","timestamp":1492530408000},"page":"2102-2113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Selective and state\u2010dependent activation of TRESK (K<sub>2P<\/sub>18.1) background potassium channel by cloxyquin"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-6369","authenticated-orcid":false,"given":"Mikl\u00f3s","family":"Lengyel","sequence":"first","affiliation":[{"name":"Department of Physiology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Dobolyi","sequence":"additional","affiliation":[{"name":"Department of Physiology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-2327","authenticated-orcid":false,"given":"G\u00e1bor","family":"Czirj\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Physiology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9541-0712","authenticated-orcid":false,"given":"P\u00e9ter","family":"Enyedi","sequence":"additional","affiliation":[{"name":"Department of Physiology Semmelweis University  Budapest 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