{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:53:32Z","timestamp":1791348812405,"version":"4.3.1"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:p>The nonsense mutations R518X-KCNQ1 and Q530X-KCNQ1 cause LQT1 (long-QT syndrome type\u00a01) and result in a complete loss of IKs channel function. In the present study we attempted to rescue the function of these mutants, in HEK (human embryonic kidney)-293 cells, by promoting readthrough of their PTCs (premature termination codons) using the pharmacological agents G-418, gentamicin and PTC124. Gentamicin and G-418 acted to promote full-length channel protein expression from R518X at 100\u00a0\u03bcM and from Q530X at 1\u00a0mM. In contrast, PTC124 did not, at any dose tested, induce readthrough of either mutant. G-418 (1\u00a0mM) treatment also acted to significantly (P&amp;lt;0.05) increase current density and peak-tail current density, at +80\u00a0mV for R518X, but not Q530X, to 58\u00b111% and 82\u00b117% of the wild-type level respectively. However, the biophysical properties of the currents produced from R518X, while similar, were not identical with wild-type as the voltage-dependence of activation was significantly (P&amp;lt;0.05) shifted by +25\u00a0mV. Overall, these findings indicate that although functional rescue of LQT1 nonsense mutations is possible, it is dependent on the degree of readthrough achieved and the effect on channel function of the amino acid substituted for the PTC. Such considerations will determine the success of future therapies.<\/jats:p>","DOI":"10.1042\/bj20111912","type":"journal-article","created":{"date-parts":[[2012,2,7]],"date-time":"2012-02-07T09:12:40Z","timestamp":1328605960000},"page":"635-642","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Readthrough of long-QT syndrome type\u00a01 nonsense mutations rescues function but alters the biophysical properties of the channel"],"prefix":"10.1042","volume":"443","author":[{"given":"Stephen\u00a0C.","family":"Harmer","sequence":"first","affiliation":[{"name":"William Harvey Heart Centre, Barts & The London School of Medicine & Dentistry, Charterhouse Square, London EC1M 6BQ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep\u00a0S.","family":"Mohal","sequence":"additional","affiliation":[{"name":"William Harvey Heart Centre, Barts & The London School of Medicine & Dentistry, Charterhouse Square, London EC1M 6BQ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Kemp","sequence":"additional","affiliation":[{"name":"William Harvey Heart Centre, Barts & The London School of Medicine & Dentistry, Charterhouse Square, London EC1M 6BQ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Tinker","sequence":"additional","affiliation":[{"name":"William Harvey Heart Centre, Barts & The London School of Medicine & Dentistry, Charterhouse Square, London EC1M 6BQ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,4,16]]},"reference":[{"key":"2021112217292484800_B1","doi-asserted-by":"crossref","first-page":"18862","DOI":"10.1073\/pnas.1010354107","article-title":"Stoichiometry of the KCNQ1\u2013KCNE1 ion channel complex","volume":"107","author":"Nakajo","year":"2010","journal-title":"Proc. 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