PMID- 25404650 OWN - NLM STAT- MEDLINE DCOM- 20150629 LR - 20181113 IS - 1643-3750 (Electronic) IS - 1234-1010 (Print) IS - 1234-1010 (Linking) VI - 20 DP - 2014 Nov 14 TI - Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation. PG - 2292-7 LID - 10.12659/MSM.892505 [doi] AB - 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/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. FAU - Li, Yao-Dong AU - Li YD AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Hong, Yi-Fan AU - Hong YF AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Zhang, Yu AU - Zhang Y AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Zhou, Xian-Hui AU - Zhou XH AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Ji, Yu-Tong AU - Ji YT AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Li, Hong-Liang AU - Li HL AD - Heart Rhythm Institute and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. FAU - Hu, Guo-Jun AU - Hu GJ AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Li, Jin-Xin AU - Li JX AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Sun, Lin AU - Sun L AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Zhang, Jiang-Hua AU - Zhang JH AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Xin, Qiang AU - Xin Q AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Yusufuaji, Yueerguli AU - Yusufuaji Y AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Xiong, Jian AU - Xiong J AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). FAU - Tang, Bao-Peng AU - Tang BP AD - Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China (mainland). LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141114 PL - United States TA - Med Sci Monit JT - Medical science monitor : international medical journal of experimental and clinical research JID - 9609063 RN - 0 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels) RN - 0 (RNA, Messenger) SB - IM MH - *Action Potentials MH - Aging/*metabolism MH - Animals MH - Atrial Fibrillation/*genetics/*physiopathology MH - Dogs MH - Gene Expression Regulation MH - Heart Atria/physiopathology MH - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/*genetics/metabolism MH - Pulmonary Veins/physiopathology MH - RNA, Messenger/genetics/metabolism MH - Refractory Period, Electrophysiological PMC - PMC4242900 EDAT- 2014/11/19 06:00 MHDA- 2015/06/30 06:00 PMCR- 2014/11/14 CRDT- 2014/11/19 06:00 PHST- 2014/11/19 06:00 [entrez] PHST- 2014/11/19 06:00 [pubmed] PHST- 2015/06/30 06:00 [medline] PHST- 2014/11/14 00:00 [pmc-release] AID - 892505 [pii] AID - 10.12659/MSM.892505 [doi] PST - epublish SO - Med Sci Monit. 2014 Nov 14;20:2292-7. doi: 10.12659/MSM.892505.