title: Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation.
abstract: BACKGROUND
  We compared cardiac electrophysiological indicators and regional expression levels of cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) channels between adult and aged dogs to identify possible mechanisms of age-related atrial fibrillation.
  
  
  METHODS
  Corrected sinus node recovery time (SNRTc) and effective refractory period (ERP) of the atrium and pulmonary veins were measured in 10 adult (3-6 years old) and 10 aged dogs (>9 years old). Expression levels of HCN2 and HCN4 channel mRNAs and proteins were measured in the sinoatrial node, atrium, and pulmonary veins by real-time PCR and Western blotting.
  
  
  RESULTS
  Aged dogs exhibited a higher induction rate of atrial fibrillation (AF) in response to electrical stimulation, longer AF duration after induction, longer SNRTc, longer right atrial effective refractory period (AERP), shorter left AERP, and increased AERP dispersion compared to adults. Expression levels of HCN2 and HCN4 channel mRNAs and proteins were lower in the sinoatrial node but higher in the atrium and pulmonary veins of aged dogs.
  
  
  CONCLUSIONS
  Changes in atrial electrophysiological indicators in aged dogs revealed sinoatrial node dysfunction. There was a reversal in the local tissue distribution of HCN2 and HCN4 channel mRNA and protein, a decrease in sinoatrial node expression, and increase in atrial and pulmonary vein expression with age. Changes in atrial electrophysiological characteristics and regional HCN channel expression patterns were associated with the onset and maintenance of age-related atrial fibrillation.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Yao-Dong
authors.initials: YD
authors.lastname: Li
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Hong
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Yu-Tong
authors.initials: YT
authors.lastname: Ji
authors.affiliation: Heart Rhythm Institute and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Hu
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Li
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xin
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Yueerguli
authors.initials: Y
authors.lastname: Yusufuaji
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Jian
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland).
authors.forename: Bao-Peng
authors.initials: BP
authors.lastname: Tang
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology*; D004285:Dogs; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000503:physiopathology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics* / Q000378:metabolism; D011667:Pulmonary Veins / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012032:Refractory Period, Electrophysiological
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D012333:RNA, Messenger