{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:21:06Z","timestamp":1788456066858,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T00:00:00Z","timestamp":1459814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Aristolochic acid (AristA) is found in plants used in traditional medicines to treat pain. We investigated the action of AristA on TREK and TRESK, potassium (K2P) channels, which are potential therapeutic targets in pain. Balkan endemic nephropathy (BEN) is a renal disease associated with AristA consumption. A mutation of TASK\u20102 (K<jats:sub>2P<\/jats:sub>5.1) channels (T108P) is seen in some patients susceptible to BEN, so we investigated how both this mutation and AristA affected TASK\u20102 channels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Currents through wild\u2010type and mutated human K2P channels expressed in tsA201 cells were measured using whole\u2010cell patch\u2010clamp recordings in the presence and absence of AristA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>TREK\u20101\u2010 and TREK\u20102\u2010mediated currents were enhanced by AristA (100\u00a0\u03bcM), whereas TRESK was inhibited. Inhibition of TRESK did not depend on the phosphorylation of key intracellular serines but was completely blocked by mutation of bulky residues in the inner pore (F145A_F352A). The TASK\u20102_T108P mutation markedly reduced both current density and ion selectivity. A related mutation (T108C) had similar but less marked effects. External alkalization and application of flufenamic acid enhanced TASK\u20102 and TASK\u20102_T108C current but did not affect TASK\u20102_T108P current. AristA (300\u00a0\u03bcM) produced a modest enhancement of TASK\u20102 current.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Enhancement of TREK\u20101 and TREK\u20102 and inhibition of TRESK by AristA may contribute to therapeutically useful effects of this compound in pain. Whilst AristA is unlikely to interact directly with TASK\u20102 channels in BEN, loss of functional TASK\u20102 channels may indirectly increase susceptibility to AristA toxicity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13465","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T01:47:42Z","timestamp":1456451262000},"page":"1639-1652","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Aristolochic acid, a plant extract used in the treatment of pain and linked to Balkan endemic nephropathy, is a regulator of K2P channels"],"prefix":"10.1111","volume":"173","author":[{"given":"Emma L","family":"Veale","sequence":"first","affiliation":[{"name":"Medway School of Pharmacy University of Kent  Kent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"Mathie","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy University of Kent  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