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"journal" : { "otype" : "Journal", "mtid" : 825, "link" : "/api/journal/825", "label" : "BRITISH JOURNAL OF PHARMACOLOGY 0007-1188 1476-5381", "pIssn" : "0007-1188", "eIssn" : "1476-5381", "reviewType" : "REVIEWED", "noIF" : false, "sciIndexed" : true, "scopusIndexed" : true, "lang" : "FOREIGN", "hungarian" : false, "published" : true, "oldId" : 825, "snippet" : true }, "volume" : "174", "issue" : "13", "firstPage" : "2102", "lastPage" : "2113", "firstPageOrInternalIdForSort" : "2102", "pageLength" : 12, "publishedYear" : 2017, "abstractText" : "BACKGROUND AND PURPOSE: Cloxyquin (5-cloroquinolin-8-ol) has been described as an activator of TRESK (K2P 18.1, TWIK-related spinal cord K+ channel) background potassium channel. We have examined the specificity of the drug by testing several K2P channels. We have investigated the mechanism of cloxyquin-mediated TRESK activation, focusing on the differences between the physiologically relevant regulatory states of the channel. EXPERIMENTAL APPROACH: Potassium currents were measured by two-electrode voltage clamp in Xenopus oocytes and by whole-cell patch clamp in mouse dorsal root ganglion (DRG) neurons. KEY RESULTS: Cloxyquin (100 microM) activated mouse and human TRESK 4.4 +/- 0.3 (n = 28) and 3.9 +/- 0.3-fold (n = 8), respectively. The drug selectively targeted TRESK in the K2P channel family and exerted state-dependent 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-coupled 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. CONCLUSIONS AND IMPLICATIONS: Cloxyquin activates TRESK by a Ca2+ /calcineurin-independent mechanism. The drug is specific for TRESK within the K2P channel family and useful for studying TRESK currents in native cells. The state-dependent pharmacological profile of this channel should be considered in the development of therapeutics for migraine and other nociceptive disorders.", "subjects" : [ { "otype" : "Classification", "mtid" : 12125, "link" : "/api/classification/12125", "label" : "Általános orvostudomány", "published" : true, "snippet" : true } ], "digital" : true, "printed" : true, "sourceYear" : 2017, "packet" : "(Lengyel Miklós (Biokémia); 2017.06.01. 13:35:16)", "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : true, "missingAuthor" : false, "oaType" : "GREEN", "oaTypeDisp" : "GREEN", "oaCheckDate" : "2024-02-28", "oaFree" : true, "oaLink" : "https://repo.lib.semmelweis.hu/handle/123456789/4836", "citationCount" : 19, "citationCountUnpublished" : 0, "citationCountWoOther" : 19, "independentCitCountWoOther" : 15, "nationalOriginCitationCount" : 4, "foreignEditionCitationCount" : 19, "doiCitationCount" : 19, "wosCitationCount" : 17, "scopusCitationCount" : 19, "wosScopusCitationCount" : 19, "wosScopusCitationCountWoOther" : 19, "wosScopusIndependentCitationCount" : 15, "wosScopusIndependentCitationCountWoOther" : 15, "independentCitationCount" : 15, "selfCitationCount" : 4, "unhandledCitationCount" : 0, "citingPubCount" : 19, "independentCitingPubCount" : 15, "citingPubCountWoOther" : 19, "independentCitingPubCountWoOther" : 15, "unhandledCitingPubCount" : 0, "citedPubCount" : 11, "citedCount" : 11, "ratings" : [ { "otype" : "SjrRating", "mtid" : 10721055, "link" : "/api/sjrrating/10721055", "label" : "sjr:D1 (2017) Scopus - Pharmacology BRITISH JOURNAL OF PHARMACOLOGY 0007-1188 1476-5381", "listPos" : 14, "rankValue" : 0.1, "type" : "journal", "ratingType" : { "otype" : "RatingType", "mtid" : 10002, "link" : "/api/ratingtype/10002", "label" : "sjr", "code" : "sjr", "published" : true, "snippet" : true }, "subject" : { "otype" : "ClassificationExternal", "mtid" : 3004, "link" : "/api/classificationexternal/3004", "label" : "Scopus - Pharmacology", "published" : true, "oldId" : 3004, "snippet" : true }, "ranking" : "D1", "calculation" : "DIRECT", "published" : true, "snippet" : true } ], "ratingsForSort" : "D1", "hasCitationDuplums" : false, "userChangeableUntil" : "2018-07-24T12:25:56.000+0000", "publishDate" : "2017-06-01T11:40:33.000+0000", "directInstitutesForSort" : "Élettani Intézet (SE / AOK / I)", "ownerAuthorCount" : 3, "ownerInstituteCount" : 5, "directInstituteCount" : 1, "authorCount" : 4, "contributorCount" : 0, "hasQualityFactor" : true, "link" : "/api/publication/3233828", "label" : "Lengyel M et al. 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