{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:13:47Z","timestamp":1793146427480,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,3,16]],"date-time":"2016-03-16T00:00:00Z","timestamp":1458086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hyperaldosteronism is associated with an increased prevalence of atrial fibrillation (AF). Mutations in\n                    <jats:italic>KCNE3<\/jats:italic>\n                    have been associated with AF, and\n                    <jats:italic>Kcne3<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice exhibit hyperaldosteronism. In this study, we used recently developed\n                    <jats:italic>Kcne3<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice to study atrial electrophysiology with respect to development of aldosterone\u2010dependent AF. In invasive electrophysiology studies,\n                    <jats:italic>Kcne3<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice displayed a reduced atrial effective refractory period (AERP) and inducible episodes of paroxysmal AF. The cellular arrhythmogenic correlate for AF predisposition was a significant increase in atrial Kv currents generated by the micromolar 4\u2010aminopyridine\u2010sensitive Kv current encoded by Kv1.5. Electrophysiological alterations in\n                    <jats:italic>Kcne3<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice were aldosterone dependent and were associated with increased Rab4, \u20105, and \u20109\u2010dependent recycling of Kv1.5 channels to the Z\u2010disc\/T\u2010tubulus region and lateral membrane\n                    <jats:italic>via<\/jats:italic>\n                    activation of the Akt\/AS160 pathway. Treatment with spironolactone inhibited Akt\/AS160 phosphorylation, reduced Rab\u2010dependent Kv1.5 recycling, normalized AERP and atrial Kv currents to the wild\u2010type level, and reduced arrhythmia induction in\n                    <jats:italic>Kcne3<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice.\n                    <jats:italic>Kcne3<\/jats:italic>\n                    deletion in mice predisposes to AF by a heretofore unrecognized mechanism\u2014namely, increased aldosterone\u2010dependent Kv1.5 recycling\n                    <jats:italic>via<\/jats:italic>\n                    Rab GTPases. The findings uncover detailed molecular mechanisms underpinning a channelopathy\u2010linked form of AF and emphasize the inevitability of considering extracardiac mechanisms in genetic arrhythmia syndromes.\u2014 Lisewski, U., Koehncke, C., Wilck, N., Buschmeyer, B., Pieske, B., Roepke, T. K. Increased aldosterone\u2010dependent Kv1.5 recycling predisposes to pacing\u2010induced atrial fibrillation in\n                    <jats:italic>Kcne3<\/jats:italic>\n                    <jats:sup>\u2010\/\u2010<\/jats:sup>\n                    mice. FASEB J. 30, 2476\u20102489 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201600317r","type":"journal-article","created":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T00:03:56Z","timestamp":1458173036000},"page":"2476-2489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Increased aldosterone\u2010dependent Kv1.5 recycling predisposes to pacing\u2010induced atrial fibrillation in\n                    <i>Kcne3<\/i>\n                    <sup>\u2010\/\u2010<\/sup>\n                    mice"],"prefix":"10.1096","volume":"30","author":[{"given":"Ulrike","family":"Lisewski","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Koehncke","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"},{"name":"Department of Cardiology, Campus Virchow Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Wilck","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Buschmeyer","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Campus Virchow Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten K.","family":"Roepke","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"},{"name":"Department of Cardiology and Angiology, Campus Mitte, Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.hrthm.2007.09.002","article-title":"Genetics of atrial fibrillation: rare mutations, common polymorphisms, and clinical relevance","volume":"5","author":"Darbar D.","year":"2008","journal-title":"Heart Rhythm"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.139"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2005.07.013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000113746"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00029330-200701020-00017"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-13-24"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2005.03.086"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/425342"},{"key":"e_1_2_7_11_1","first-page":"1735","article-title":"[KCNE3 R53H substitution in familial atrial fibrillation]","volume":"118","author":"Zhang D. 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