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Two-way concentration-dependent effect of H2O2 on Ikur and Ica,L in human atrial myocytes
Author(s): 
Pages: 695-703
Year: Issue:  6
Journal: Acta Physiologica Sinica

Keyword:  氧化应激心肌心房颤动离子通道抗氧化剂;
Abstract: 本实验旨在观察活性氧(reactive oxygen species,ROS)对人心房肌细胞电生理活动特性的影响.取有心房颤动(atrial fibrillation,AF)和非AF心脏手术患者(各12例)右心耳组织,用酶消化法得到单个心房肌细胞.两组细胞(每组n=75)分别随机分为三个亚组:对照组(n=12)、H2O2组(0.1、0.2、0.5、0.75、1、2、5、10 μmol/L H2O2,每个浓度n=7)和维生素C(ROS清除剂)组(1 μmol/L维牛素C,n=7).实验采用全细胞膜片钳方法记录电生理活动.与非AF对照组相比,AF对照组超快速延迟整流钾电流(ultrarapid delayed rectifier K+ current,IKur)和L-型钙电流(L-type calcium current,ICa.L)电流密度(pA/pF)均明显降低(6.27±0.67 vs 3.77±0.56,P<0.05;6.31±0.60 vs 3.34±0.32,P<0.05),动作电位时程(action potential duration,APD)(ms)也明显缩短(405±13 vs 354±12,P<0.05).在非AF和AF组中,H2O2对心房肌细胞IKur和ICa.L的电流密度均有浓度依赖性双向影响--高抑低促.非AF组中,H2O2浓度为0.2μmol/L时有最人增强作用,而0.75 μmol/L为分界浓度,大于0.75 Ixmol/L时,随H2O2浓度增加Ikur和ICa,L的电流密度逐渐降低:在另一方面,0.2、1、2、5和10μmol/L H2O2 孵育的心房肌细胞APD90与同组对照组相比均明显缩短(P<0.05),而与AF对照组相比无明显差异.在AF组中,H2O2的最大效应浓度为0.5 μmol/L,而1 μmol/L为分界浓度.维生素C可以逆转H2O2的日述作用,但单独给予维生素C并不改变通道特性.H202诱导正常人心房肌细胞发牛电生理活动特性改变与AF时心肌电重构(atrial electrical remodeling,AER)相似,显示ROS可能诱发AF;同时,H2O2又能加重AF时AER,对AF有维持作用.以上结果提示ROS清除剂可能对预防和治疗AF有重要意义.
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