{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:46:30Z","timestamp":1791351990722,"version":"4.3.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,12,17]]},"abstract":"\n Background<\/jats:title>\n \n The mouse ether\u2010a\u2010go\u2010go\u2010related gene 1a (\n \n mERG<\/jats:styled-content>\n 1a,\n mKCNH<\/jats:styled-content>\n 2\n <\/jats:italic>\n ) encodes\n mERG<\/jats:styled-content>\n K\n +<\/jats:sup>\n channels in mouse cardiomyocytes. The\n mERG<\/jats:styled-content>\n channels and their human analogue,\n hERG<\/jats:styled-content>\n channels, conduct I\n Kr<\/jats:sub>\n . Mutations in\n hERG<\/jats:styled-content>\n channels reduce I\n Kr<\/jats:sub>\n to cause congenital long\u2010QT syndrome type 2, mostly by decreasing surface membrane expression of trafficking\u2010deficient channels. Three\n cDNA<\/jats:styled-content>\n sequences were originally reported for\n mERG<\/jats:styled-content>\n channels that differ by 1 to 4 amino acid residues (\n mERG<\/jats:styled-content>\n \u2010London,\n mERG<\/jats:styled-content>\n \u2010Waterston, and\n mERG<\/jats:styled-content>\n \u2010Nie). We characterized these\n mERG<\/jats:styled-content>\n channels to test the postulation that they would differ in their protein trafficking and biophysical function, based on previous findings in long\u2010QT syndrome type 2.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n The 3\n mERG<\/jats:styled-content>\n and\n hERG<\/jats:styled-content>\n channels were expressed in HEK293 cells and neonatal mouse cardiomyocytes and were studied using Western blot and whole\u2010cell patch clamp. We then compared our findings with the recent sequencing results in the Welcome Trust Sanger Institute Mouse Genomes Project (WTSIMGP).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n First, the\n mERG<\/jats:styled-content>\n \u2010London channel with amino acid substitutions in regions of highly ordered structure is trafficking deficient and undergoes temperature\u2010dependent and pharmacological correction of its trafficking deficiency. Second, the voltage dependence of channel gating would be different for the 3\n mERG<\/jats:styled-content>\n channels. Third, compared with the WTSIMGP data set, the\n mERG<\/jats:styled-content>\n \u2010Nie clone is likely to represent the wild\u2010type mouse sequence and physiology. Fourth, the WTSIMGP analysis suggests that substrain\u2010specific sequence differences in\n mERG<\/jats:styled-content>\n are a common finding in mice. These findings with\n mERG<\/jats:styled-content>\n channels support previous findings with\n hERG<\/jats:styled-content>\n channel structure\u2013function analyses in long\u2010QT syndrome type 2, in which sequence changes in regions of highly ordered structure are likely to result in abnormal protein trafficking.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.001491","type":"journal-article","created":{"date-parts":[[2014,12,12]],"date-time":"2014-12-12T02:52:49Z","timestamp":1418352769000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Mouse ERG K\n +<\/sup>\n Channel Clones Reveal Differences in Protein Trafficking and Function"],"prefix":"10.1161","volume":"3","author":[{"given":"Eric C.","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke M.","family":"Moungey","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evi","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah P.","family":"Concannon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey L.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Kyle","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Makielski","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadguna Y.","family":"Balijepalli","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig T.","family":"January","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90340-2"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7604285"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.5.870"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6535"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.33.21061"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206569200"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000079028.31393.15"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.570200"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2009.05150.x"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00494.2010"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.047290"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0828-282X(09)70117-5"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2008.12.887"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00891.2003"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1422-05.2005"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01262"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.8.5997"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5350fje"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.3438"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5265.1087.c"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01236.2009"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00008.2002"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00777.2005"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.44.31123"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.4.H1748"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3181dab014"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(01)00127-X"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.118745"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.062588"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411042200"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-003-2270-3"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2004.02.003"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00183.2002"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2003.12.006"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2008.10.011"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-19"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10413"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.114.001491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:39:01Z","timestamp":1715596741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.114.001491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,17]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,12,17]]}},"alternative-id":["10.1161\/JAHA.114.001491"],"URL":"https:\/\/doi.org\/10.1161\/jaha.114.001491","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,17]]},"assertion":[{"value":"2012-11-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e001491"}}