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14 November 2014 : Original article  

Association between Reversal in the Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel and Age-Related Atrial Fibrillation

Yao-Dong LiABCDEFG, Yi-Fan HongABCDEF, Yu ZhangABCDEFG, Xian-Hui ZhouABCDEFG, Yu-Tong JiBC, Hong-Liang LiA, Guo-Jun HuB, Jin-Xin LiC, Lin SunD, Jiang-Hua ZhangB, Qiang XinF, Yueerguli YusufuajiB, Jian XiongD, Bao-Peng TangA

DOI: 10.12659/MSM.892505

Med Sci Monit 2014; 20:2292-2297


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.

MATERIAL AND 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.

Keywords: Aging - metabolism, Action Potentials, Atrial Fibrillation - physiopathology, Dogs, Gene Expression Regulation, Heart Atria - physiopathology, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism, Pulmonary Veins - physiopathology, RNA, Messenger - metabolism, Refractory Period, Electrophysiological



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Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.938532

Med Sci Monit 2022; 28:e938532


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750