AT1-Calcineurin信号通路对肥大乳鼠心房肌细胞内向整流钾离子通道重构的调控作用  

Regulation of AT1-Calcineurin signaling pathway on inward rectifier potassium ionic channel remolding of hypertrophic atrial myocytes from neonatal rats

作　　者：何炯红[1] 杨龙[1] 杨永曜[1] 李隽[1] 邓娜[1] 田银[1] 杨英[1] HE Jionghong YANG Long YANG Yongyao LI Jun DENG Na TIAN Yin YANG Ying(Guizhou Provincial People＇s Hospital, Guiyang, 550002, Chin)

机构地区：[1]贵州省人民医院,贵阳550002

出　　处：《临床心血管病杂志》2016年第10期1047-1051,共5页Journal of Clinical Cardiology

基　　金：国家自然科学基金资助项目(No:81060018;81260040);贵州省科学技术基金(No:黔科合J字[2012]2239号)

摘　　要：目的:探讨血管紧张素Ⅱ受体1型(AT1)-钙调神经磷酸酶(CaN)信号通路对肥大乳鼠心房肌细胞内向整流钾电流(IK1)离子通道重构和动作电位时程(APD)改变的调控作用。方法:酶解法分离获得1d龄SD乳鼠心房肌细胞,据干预方式不同分为4组:对照组;牵张肥大组:牵张刺激24h;替米沙坦组:1μmol/L替米沙坦干预1h,牵张24h;环孢素(CsA)组:0.25μg/ml CsA干预1h,牵张24h。免疫印记法检测Kir2.1、CaN A亚基表达。全细胞膜片钳技术检测细胞膜IK1和单细胞APD的变化。结果:牵张刺激导致心房肌细胞肥大,促进CaN A亚基和Kir2.1蛋白表达,增大IK1电流密度,缩短动作电位复极50%(APD50)和复极90%(APD90);CsA和替米沙坦干预显著抑制牵张刺激的上述效应。结论:AT1-CaN信号通路参与调控肥大乳鼠心房肌细IK1离子通道重构和APD改变。Objective：To investigate the role of angiotensin Ⅱ receptor 1type（AT1）-calcineurin（CaN）signaling pathway in inward rectifier potassium current（IK1）ionic channel remolding and action potential（AP）change of hypertrophic atrial myocytes from neonatal rats.Method：The atrial myocytes were isolated from 1-d-old SD rats and cultured on silicone sheeting for 24 h,and they were divided into 4groups depending on the treatment administered：Control,Stretch-induced hypertrophy（Stretched;cells were stretched for 24h）,Telmisartan（cells were incubated with 1μmol/L Telmisartan for 1hthen stretched for 24h）,and Cyclosporin-A（CsA;cells were incubated with 0.25μg/ml CsA for 1hthen stretched for 24h）groups.The proteins expression of kir2.1and CaN A subunit（CaNA）were assayed by western blot analysis.IK1 and AP were recorded by whole-cell patch clamp technique.Result：Stretch stimulation lead to atrial myocyte hypertrophy,promoted the expression of kir2.1and CaNA proteins,increased the density of IK1,and shorten the AP duration（APD）at 50% and 90%level of repolarization,which were significantly attenuated by incubation with Telmisartan and CsA.Conclusion：AT1-CaN signaling pathway plays an important role in regulating IK1 ionic channel remolding and AP change of stretch-induced hypertrophic atrial neonatal myocytes.

关 键 词：心房肌细胞 钾电流 动作电位 重构 全细胞膜片钳技术 

分 类 号：R541.7[医药卫生—心血管疾病]