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Two--way concentration--dependent effect of H_(2)O_(2) on I_(Kur) and I_(Ca,L) in human atrial myocytes

Zhang Guangwei, Gu Tianxiang, Wang Chun, Yu Lei, Wen Ti

Department of Cardiac Surgery,the First Hospital of China Medical University.Shenyang 110001,Liaoning；China

Abstract

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),H_(2)O_(2) group(0.1,0.2,0.5,0.75,1,2,5,10 #mu#mol/L,n=7 at each concentration) and vitamin C(antioxidant) group(1 #mu#mol/L,n=7).Ultrarapid delayed rectifier K~(+) current(I_(Kur)),L-type calcium current(I_(Ca,L)) and action potential duration(APD) were recorded by whole-cell patch clamp.In AF control group,the maximum current densities of I_(Kur) and I_(Ca,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 non-AF and AF groups,H_(2)O_(2) showed two-way concentration-dependent effect on I_(Kur) and I_(Ca,L).The maximum current densities of I_(Kur) and I_(Ca,L) was significantly increased at lower H_(2)O_(2) concentration,but was decreased at higher H_(2)O_(2) concentration.In non-AF group,0.2 #mu#mol/L H_(2)O_(2) caused a peak increase in the maximum currunt dentities of I_(Kur) [(8.92±0.51) pA/pF,P<0.05] and I_(Ca,L) [(9.32±0.67) pA/ pF,P<0.05].H_(2)O_(2) at a concentration higher than 0.75 #mu#mol/L decreased I_(Kur) and I_(Ca,L).When the H_(2)O_(2) concentrations were 0.2,1,2,5 and 10 #mu#mol/L,APD_(90) 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 H_(2)O_(2) was 0.5 #mu#mol/L,and the turning concentration was 1 #mu#mol/L.The H_(2)O_(2) concentration-current density curve in AF group was similar to that in non-AF group,but the turning point shifted to the right,indicating that the way that H_(2)O_(2) acted on ion channels in AF was the same as that in non-AF,however,the sensitivity of ion channels to H_(2)O_(2) was decreased in AF.Vitamin C reversed these changes induced by H_(2)O_(2),and did not affect the characteristics of ion channels.H_(2)O_(2)-induced electrophysiological changes in human atrial myocytes were similar to atrial electrical remodeling(AER) in AF,suggesting that ROS might induce AF.Meanwhile,H_(2)O_(2) also could aggravate AER in AF,contrib-uting to the maintenance of AF.The results suggest that antioxidants might play a significant role in the prevention and treatment of AF.

Key words: oxidative stress;cardiac myocyte;atrial fibrillation;ion channels;antioxidants

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Citing This Article：

Zhang Guangwei, Gu Tianxiang, Wang Chun, Yu Lei, Wen Ti. Two--way concentration--dependent effect of H_(2)O_(2) on I_(Kur) and I_(Ca,L) in human atrial myocytes. Acta Physiol Sin 2008; 60 (6): 695-703 (in Chinese with English abstract).