title: The E23K variant of the Kir6.2 subunit of the ATP-sensitive potassium channel increases susceptibility to ventricular arrhythmia in response to ischemia in rats.
abstract: BACKGROUND
  The E23K variant of the Kir6.2 subunit of the ATP-sensitive potassium (KATP) channel has been implicated in cardiac remodeling. However, the effects of E23K variant on ventricular electrophysiology and arrhythmogenesis remain unclear.
  
  
  METHODS
  Transgenic rats were generated to express human E23K-variant genomic DNA in the heart under the α-myosin heavy chain promoter. Electrophysiological parameters including electrocardiograph, ventricular action potential duration (APD), effective refractory period (ERP), electrical alternans and ventricle arrhythmia threshold were examined in wild type (WT) and transgenic rats. The KATP current in cardiomyocytes was recorded using whole-cell patch clamp techniques.
  
  
  RESULTS
  No differences in the electrophysiological parameters between the two groups were found at baseline. However, after acute ischemic stress, shortened QT intervals were further aggravated in the E23K-variant rats. Additionally, the E23K variant exacerbated the decrease of APD70, APD90and ERP. The ventricular arrhythmia and alternans thresholds were significantly attenuated, and the duration of ventricular arrhythmia induced by electrical stimulation was significantly prolonged in the E23K-variant rats. More importantly, the KATP current in cardiomyocytes was significantly increased in the E23K-variant rats after ischemia.
  
  
  CONCLUSIONS
  The E23K variant of the KATP channel increased the susceptibility to ventricular arrhythmia under acute ischemia stress.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China; Department of Emergency Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
authors.forename: Menglong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
authors.forename: Menglin
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China; Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, United States.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address: wanjun1963@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005786:Gene Expression Regulation; D005838:Genotype; D006352:Heart Ventricles / Q000503:physiopathology; D054086:KATP Channels / Q000096:biosynthesis / Q000235:genetics; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D055647:Rats, Transgenic; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling; D000099161:Kcnj11 Channel
chemical_list: D004247:DNA; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel
keywords: ATP-sensitive potassium channel; E23K variant; Ischemia; Transgenic model; Ventricular arrhythmia