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H2O2对人心房肌细胞IKur和ICa.L的浓度依赖性双向影响 被引量:4

Two-way concentration-dependent effect of H_2O_2 on I_(Kur) and I_(Ca,L) in human atrial myocytes
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摘要 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、10μmol/LH2O2,每个浓度n=7)和维生素C(ROS清除剂)组(1μmol/L维生素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±0.67vs3.77±0.56,P<0.05;6.31±0.60vs3.34±0.32,P<0.05),动作电位时程(action potential duration,APD)(ms)也明显缩短(405±13vs354±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时有最大增强作用,而0.75μmol/L为分界浓度,大于0.75μmol/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/LH2O2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0.5μmol/L,而1μmol/L为分界浓度。维生素C可以逆转H2O2的上述作用,但单独给予维生素C并不改变通道特性。H2O2诱导正常人心房肌细胞发生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。 It has been shown that oxidative stress correlates with atrial fibrillation (AF). The purpose of the present study was to investigate the effects of reactive oxygen species (ROS) on the electrophysiological activity of human atrial myocytes. Right atrial appendages were obtained from patients with AF (AF group, n=12) and without AF (non-AF group, n=12). Single human atrial myocytes were isolated through enzymatic dissociation with type XXIV protease and type V collagenase, then divided into three subgroups: control group (n=12), H2O2 group (0.1, 0.2, 0.5, 0.75, 1, 2, 5, 10 μmol/L, n=7 at each concentration) and vitamin C (antioxidant) group (1 μmol/L, n=7). Ultrarapid delayed rectifier K^+ current (IKur), L-type calcium current (ICa,L) and action potential duration (APD) were recorded by whole-cell patch clamp. In AF control group, the maximum current densities of IKw and ICa,L were significantly lower than that in non-AF control group (both P〈0.05) and APD90 was significantly shorter as well (P〈0.05). In both nonAF and AF groups, H2O2 showed two-way concentration-dependent effect on 1Kw and ICa,L. The maximum current densities of IKw and /Ca.L was significantly increased at lower H2O2 concentration, but was decreased at higher H2O2 concentration. In non-AF group, 0.2 μmol/L H2O2 caused a peak increase in the maximum currunt dentities of Inur [(8.92±0.51) pA/pF, P〈0.05] and ICa.L [(9.32±0.67) pA/ pF, P〈0.05]. H2O2 at a concentration higher than 0.75 μmol/L decreased IKw and ICa.L. When the Hat2 concentrations were 0.2, 1, 2, 5 and 10 μmol/L, APD90 was significantly shorter compared with that in non-AF control group (P〈0.05), meanwhile it had no significant difference from that in AF control group. In AF group, the peak effective concentration of H2O2 was 0.5 μmol/L, and the turning concentration was 1 μmol/L. The H2O2 concentration-current density curve in AF group was similar to that in non-AF group, hut the turning point shifted to the right, indicating that the way that H2O2 acted on ion channels in AF was the same as that in non-AF, however, the sensitivity of ion channels to H2O2 was decreased in AE Vitamin C reversed these changes induced by H2O2, and did not affect the characteristics of ion channels. H2O2-induced electrophysiological changes in human atrial myocytes were similar to atrial electrical remodeling (AER) in AF, suggesting that ROS might induce AE Meanwhile, H2O2 also could aggravate AER in AE contributing to the maintenance of AF. The results suggest that antioxidants might play a significant role in the prevention and treatment of AF.
出处 《生理学报》 CAS CSCD 北大核心 2008年第6期695-703,共9页 Acta Physiologica Sinica
基金 supported by the National Natural Science Foundation of China(No.39700059) Sciences Foundation of Educational Department of Liaoning Province,China(No.20122148)
关键词 氧化应激 心肌 心房颤动 离子通道 抗氧化剂 oxidative stress cardiac myocyte, atrial fibrillation ion channels antioxidants
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