{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:53:47Z","timestamp":1790016827242,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T00:00:00Z","timestamp":1384300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL079275"],"award-info":[{"award-number":["HL079275"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL034215"],"award-info":[{"award-number":["HL034215"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008476","name":"University of California, Irvine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008476","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":[[2014,2]]},"abstract":"\n Mutations in the human\n KCNE3<\/jats:italic>\n potassium channel ancillary subunit gene are associated with life\u2010threatening ventricular arrhythmias. Most genes underlying inherited cardiac arrhythmias, including\n KCNE3,<\/jats:italic>\n are not exclusively expressed in the heart, suggesting potentially complex disease etiologies. Here we investigated mechanisms of\n KCNE3<\/jats:italic>\n \u2010linked arrhythmogenesis in\n Kcne3<\/jats:italic>\n \u2010\/\u2010<\/jats:sup>\n mice using real\u2010time qPCR, echo\u2010 and electrocardiography, ventricular myocyte patch\u2010clamp, coronary artery ligation\/reperfusion, blood analysis, cardiac synaptosome exocytosis, microarray and pathway analysis, and multitissue histology.\n Kcne3<\/jats:italic>\n transcript was undetectable in adult mouse atria, ventricles, and adrenal glands, but\n \n Kcne3\n \u2010\/\u2010<\/jats:sup>\n <\/jats:italic>\n mice exhibited 2.3\u2010fold elevated serum aldosterone (\n P<\/jats:italic>\n = 0.003) and differentially expressed gene networks consistent with an adrenal\u2010targeted autoimmune response. Furthermore, 8\/8\n \n Kcne3\n \u2010\/\u2010<\/jats:sup>\n <\/jats:italic>\n mice\n vs.<\/jats:italic>\n 0\/8 Kcne3\n +\/+<\/jats:sup>\n mice exhibited an activated\u2010lymphocyte adrenal infiltration (\n P<\/jats:italic>\n =0.0002).\n Kcne3<\/jats:italic>\n deletion also caused aldosterone\u2010dependent ventricular repolarization delay (19.6% mean QT\n c<\/jats:sub>\n prolongation in females;\n P<\/jats:italic>\n <0.05) and aldosterone\u2010dependent predisposition to postischemia arrhythmogenesis. Thus, 5\/11\n \n Kcne3\n \u2010\/\u2010<\/jats:sup>\n <\/jats:italic>\n mice\n vs.<\/jats:italic>\n 0\/10 Kcne3\n +\/+<\/jats:sup>\n mice exhibited sustained ventricular tachycardia during reperfusion (\n P<\/jats:italic>\n <0.05).\n Kcne3<\/jats:italic>\n deletion is therefore arrhythmogenic by a novel mechanism in which secondary hyperaldosteronism, associated with an adrenal\u2010specific lymphocyte infiltration, impairs ventricular repolarization. The findings highlight the importance of considering extracardiac pathogenesis when investigating arrhythmogenic mechanisms, even in inherited, monogenic channelopathies.\u2014Hu, Z., Crump, S. M., Anand, M., Kant, R., Levi, R., Abbott, G. W.\n Kcne3<\/jats:italic>\n deletion initiates extracardiac arrhythmogenesis in mice.\n FASEB J.<\/jats:italic>\n 28, 935\u2013945 (2014).\n www.fasebj.org<\/jats:ext-link>\n <\/jats:p>","DOI":"10.1096\/fj.13-241828","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:53:00Z","timestamp":1384390380000},"page":"935-945","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Kcne3<\/i>\n deletion initiates extracardiac arrhythmogenesis in mice"],"prefix":"10.1096","volume":"28","author":[{"given":"Zhaoyang","family":"Hu","sequence":"first","affiliation":[{"name":"Bioelectricity Laboratory University of California Irvine California USA"},{"name":"Department of Pharmacology University of California Irvine California USA"},{"name":"Department of Physiology and Biophysics School of Medicine University of California Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn M.","family":"Crump","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory University of California Irvine California USA"},{"name":"Department of Pharmacology University of California Irvine California USA"},{"name":"Department of Physiology and Biophysics School of Medicine University of California Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Anand","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory University of California Irvine California USA"},{"name":"Department of Pharmacology University of California Irvine California USA"},{"name":"Department of Physiology and Biophysics School of Medicine University of California Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Kant","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory University of California Irvine California USA"},{"name":"Department of Pharmacology University of California Irvine California USA"},{"name":"Department of Physiology and Biophysics School of Medicine University of California Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Levi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey W.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory University of California Irvine California USA"},{"name":"Department of Pharmacology University of California Irvine California USA"},{"name":"Department of Physiology and Biophysics School of Medicine University of California Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-012-0287-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62928"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.06.018"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-173682"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.3.H747"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-110171"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.2.378"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.12.76"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.047829"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25713"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35876"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5699"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5448"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12285562"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2006.11.015"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.20762"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000289"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141233398"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.503706"},{"key":"e_1_2_7_21_1","first-page":"36","article-title":"B lymphocytic clonal expansion in rheumatoid arthritis","volume":"23","author":"McGee B.","year":"1996","journal-title":"J. Rheumatol."},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.4161\/chan.23258","article-title":"KCNE gene expression is dependent on the proliferation and mode of activation of leukocytes","volume":"7","author":"Sole L.","year":"2013","journal-title":"Channels (Austin)"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.107.748103"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-12-0551"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20834"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(96)00448-1"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.134809"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0151k.x"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.13-241828","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.13-241828","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.13-241828","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:43:58Z","timestamp":1761695038000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.13-241828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,13]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1096\/fj.13-241828"],"URL":"https:\/\/doi.org\/10.1096\/fj.13-241828","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,13]]},"assertion":[{"value":"2013-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}