中国病理生理杂志2025,Vol.41Issue(10):1873-1881,9.DOI:10.3969/j.issn.1000-4718.2025.10.001
钾电流重构在老年小鼠房颤发生中的作用及其机制
Characteristics of potassium current remodeling of atrial myocytes in aged mice with atrial fibrillation
摘要
Abstract
AIM:To observe the changes of atrial fibrillation susceptibility,and the remodeling of atrial myo-cyte action potential,ultrarapid activation delayed rectifier potassium current(IKur)and transient outward potassium cur-rent(Ito)in elderly mice,and to explore the mechanism of atrial fibrillation from the single cell electrophysiological level.METHODS:The C57BL/6J mice were divided into old group(20 months old)and young group(4 months old).Atrial fi-brillation was induced by esophageal atrial pacing.The atrial myocytes were isolated,and action potential and ion currents were recorded with patch-clamp technique.The associated proteins were detected by Western blot technique.RE-SULTS:(1)Compared with young mice,the total incidence of atrial fibrillation was significantly increased in old mice(20.0%at 4 months old vs 60.0%at 20 months old,P<0.01).(2)The action potential duration of atrial myocytes in aged mice was shortened,and more significantly after stimulation.(3)The density of Ito and IKur in atrial myocytes of aged mice increased significantly,from(12.6±1.4)pA/pF to(21.7±1.1)pA/pF,and from(7.5±1.5)pA/pF to(13.3±2.1)pA/pF,respectively(P<0.01).After stimulation,the current increased more significantly,especially in older atrial cells.Compared with the young mice,the steady-state activation curve of Ito in the atrial myocytes of the aged mice shifted towards the depolarization,suggesting that activation of Ito channels in the aged mice increased at the same voltage stimula-tion.(4)Compared with young group,the expression of KV4.2(generating Ito)and KV1.5(generating IKur)proteins in the atrial tissue of the mice in old group was significantly increased,and the expression of caveolin-3 and end-binding protein 1(EB1)was up-regulated,suggesting that the increases in KV4.2 and KV1.5 total channel proteins and effective proteins in the cell membrane might contribute to the increase in the remodeling of potassium currents in the elderly atrial myo-cytes.CONCLUSION:The incidence of atrial fibrillation in elderly mice is significantly augmented,which may be related to the increases in Ito and IKur in atrial myocytes.The remodeling of potassium currents in elderly atrial myocytes is one of the electrophysiological bases leading to the shortening of action potential duration and the occurrence of atrial fibrillation.关键词
老年小鼠/心房颤动/心房肌细胞/瞬时外向钾电流/超速激活延迟整流钾电流Key words
aged mice/atrial fibrillation/atrial myocytes/transient outward potassium current/ultrarapid ac-tivated delayed rectifier potassium current分类
临床医学引用本文复制引用
董颖,陈雅婷,李彬,苗祖霈,但晴,王雪萍,薛桥,李泱..钾电流重构在老年小鼠房颤发生中的作用及其机制[J].中国病理生理杂志,2025,41(10):1873-1881,9.基金项目
国家自然科学基金资助项目(No.82370327 ()
No.81870249) ()