Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation.
Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation.
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DOI：
10.12659/msm.892505
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发表时间：
2014-11-14
期刊：
影响因子：
--
通讯作者：
Tang BP
中科院分区：
文献类型：
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作者：
Li YD;Hong YF;Zhang Y;Zhou XH;Ji YT;Li HL;Hu GJ;Li JX;Sun L;Zhang JH;Xin Q;Yusufuaji Y;Xiong J;Tang BP
我们比较了成年狗和老年狗的心脏电生理指标和心脏超极化激活的环核苷酸门控（HCN）通道的区域表达水平，以确定年龄相关性心房颤动的可能机制。测定10只成年犬（3 ~ 6岁）和10只老年犬（10 ~ 9岁）心房和肺静脉的窦房结矫正恢复时间（SNRTc）和有效不应期（ERP）。采用实时荧光定量PCR和Western blotting检测HCN2和HCN4通道mrna和蛋白在窦房结、心房和肺静脉中的表达水平。老年犬在电刺激下心房颤动（AF）诱发率较高，诱发后AF持续时间较长，SNRTc较长，右心房有效不应期（AERP）较长，左心房有效不应期较短，且AERP弥散度增加。老年犬HCN2和HCN4通道mrna和蛋白的表达水平在窦房结中较低，而在心房和肺静脉中较高。老年犬心房电生理指标变化提示窦房结功能障碍。随着年龄的增长，HCN2和HCN4通道mRNA和蛋白的局部组织分布发生逆转，窦房结表达减少，心房和肺静脉表达增加。心房电生理特征和区域HCN通道表达模式的变化与年龄相关性心房颤动的发生和维持有关。
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. 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. 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. 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.