title: Human KCNQ1 S140G mutation is associated with atrioventricular blocks.
abstract: BACKGROUND
  We recently reported that an S140G mutation in human KCNQ1, an alpha subunit of potassium channels, was involved in the pathogenesis of familial atrial fibrillation (AF), but it is not clear whether the mutation is associated with other cardiac arrhythmias.
  
  
  OBJECTIVE
  The purpose of this study was to further explore the association of the KCNQ1 S140G mutation with cardiac arrhythmias.
  
  
  METHODS
  We produced a transgenic mouse model with myocardium-specific expression of the human KCNQ1 S140G mutation under the control of an alpha-cardiac myosin heavy chain promoter by standard transgenic procedure and evaluated the relationship between the KCNQ1 mutation and its phenotypes in a human family.
  
  
  RESULTS
  Four lines of transgenic mice were established with a high level of human KCNQ1 S140G expression in the heart. Frequent episodes of first-, second-, advanced-, or third-degree atrioventricular block (AVB) occurred in at least 65% of transgenic descendants from the four lines. However, none of the five wild-type transgenic lines presented with AVBs. HMR1556, a KCNQ1-specific blocker, can terminate the AVBs. With the exception of at most three AF individuals, at least 13 AF patients were found to show obviously slow ventricular response, which may be one manifestation of AVBs. Interestingly, AF was not detected in these transgenic mice.
  
  
  CONCLUSIONS
  The results suggest that human KCNQ1 S140G is also likely to be a causative mutation responsible for AVBs. The transgenic mouse model is a potential tool to explore mechanisms of AVBs.
authors.affiliation: Department of Cardiology, Tongji Hospital, Shanghai, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiongjian
authors.initials: X
authors.lastname: Dong
authors.forename: Ying
authors.initials: Y
authors.lastname: Kuang
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Su
authors.forename: Luying
authors.initials: L
authors.lastname: Peng
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Jin
authors.forename: Yusong
authors.initials: Y
authors.lastname: He
authors.forename: Ban
authors.initials: B
authors.lastname: Liu
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Lin
authors.forename: Qinshu
authors.initials: Q
authors.lastname: Zhou
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.forename: Petra M H
authors.initials: PM
authors.lastname: Eurlings
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.forename: Yi Han
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics / Q000503:physiopathology; D001283:Atrioventricular Node / Q000187:drug effects / Q000503:physiopathology; D002681:China; D002839:Chromans / Q000494:pharmacology; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D005998:Glycine; D006327:Heart Block / Q000235:genetics* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D051657:KCNQ1 Potassium Channel / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012107:Research Design; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002839:Chromans; C420023:HMR 1556; D051657:KCNQ1 Potassium Channel; D013449:Sulfonamides; D012694:Serine; D005998:Glycine