| Background and objectivesDefinition of Oxidative stress is cells are injured by excessive oxidation when promotiong oxidation and oxidation resistence are not balanced in cells. Atrial fibrillation is one of the most common arrhythmia. Mechanism of atrial fibrillation is interrelated with electrical remodling, tissue remodling and ion channel remodling. Many studies show oxdative stress and atrail fibrillation have very close relationship. But the relationship are not clear. We do not know oxidative stress plays real role and degree of effects in the atrail fibrillation. This study use low concentration H2O2make oxidative stress injured model in rabbit atrail myocytes, deeply understand the mechanism of electrical changed in rabbit atrial myocytes by oxidative stress, and study protective mechanism of piperine in cells’electricity. On the other hand, we study protective effects of apocynin in oxidative ingured in cells’electricity. We can know the relationship between cause and effect in atrial fibrillation and oxidative stress, deeply understand mechanism of atrial fibrillation, and have basis on prevention of atrial fibrillation.MethodsIsolated rabbit atrial myoeytes by using enzymatie method. Selected rabbit single atrial myocyte which was in good condition and caleium—resistant. Established of whole—cell Patch clamp mode. Applicated H2O250μmol/Las a tool for medieine, to establish a cell model of oxidative stress. And applicated7μmol/L PIP and100μg/ml APO as two drugs for protecting.1. Recorded AP, ICa L, Ito, IK1and IKur of rabbit single atrial myocyte in oxidative stress by Patch and study the protective effects of PIP.2. Recorded Ito and IKur of rabbit single atrial myocyte in oxidative stress by Patch and study the protective effects of APO.Results1. PIP(7μmol/L) had no significant effect on APD and ICa L of normal single rabbit atrial myocyte as well as its channel dynamics. In presence of50μmol/L H2O2, APD50and APD90shortened (P<0.01), amplitude of resting membrane potential(RMP) decreased (P<0.05), the peak of ICa,L reduced significantly (P<0.05), the Ⅰ-Ⅴ curve shifted upward, the steady-state activation curve of ICa,L was shifted to positive potentials, the steady—state inactivation was shifted to negative potentials, but recovery from the inactivation of ICa,L showed no remarkable changes.PIP (7μmol/L) significantly alleviated the inhibiting effect of H2O2on APD and ICa,L (P<0.01) and protected the changes of ICa,L dynamics induced by H2O2.2. Piperine (7μmol/L) had no significant effect on Ito and its channel dynamics. In presence of50μmol/L H2O2, the peak current of Ito reduced significantly(P<0.05), the I—V curve shifted downward, the steady—state activation curve of Ito was shifted positive potentials, steady—state inactivation and recovery from inactivation of Ito were not markedly changed. The closed—state inactivation of Ito was accelerated. Piperine (7μmol/L) alleviated the inhibiting effect of H2O2on Ito significantly (P<0.01). In addition, piperine protected the changes of Ito dynamics induced by H2O2.3. Piperine (7μmol/L) had no significant effect on IK1and IKur and their channel dynamics. In presence of50μmol/L H2O2, the peak current of IK1reduced significantly (P<0.05); the peak current of IKur reduced significantly (P<0.05), the steady—state activation curve of IKur was shifted right, the steady—state inactivation curve of IKur was shifted left and recovery from inactivation of IKurwas shifted downward. The IKur has the frequency—dependent characteristics. Piperine (7μmol/L) alleviated the inhibiting effect of H2O2on IK1and IKur significantly (P<0.01). In addition, piperine protected the changes of IKur dynamics induced by H2O2.4. Apocynin (100μg/ml) had no significant effect on IKUr, Ito and their channel dynamics. In the presence of50μmol/L H2O2, the peak current of IKur reduced significantly (P<0.05), the Ⅰ—Ⅴ curve shifted downward, the peak current of Ito reduced significantly (P<0.05), the Ⅰ—Ⅴ curve shifted downward, the steady—state activation curve of Ito was shifted positive potentials, steady—state inactivation and recovery from inactivation of Ito did not change markedly. The closed—state inactivation of Ito was accelerated. Apocynin (100μg/ml) alleviated the inhibiting effect of H2O2on IKUr and Ito significantly (P<0.01). In addition, apocynin protected the changes of Ito dynamics induced by H2O2.Conclusions1. H2O2can shorten APD50and APD90markedly, decrease amplitude of RMP, and change APA very little. PIP can partly regain the changed.2. H2O2can inhibit ICa L markedly, slow the activation of ICa,L, accelerate the inactivation of ICa,L, have no effects on recovery from the inactivation of ICa,L. PIP can partly regain the changed.3. H2O2can inhibit IK1. PIP can partly regain the changed.4. H2O2can inhibit Ito markedly, slow the activation of Ito, increase the closed—state inactivation of Ito, have no effects on inactivation and recovery from the inactivation of Ito. PIP can partly regain the changed.5. H2O2can inhibit IKUr markedly, slow the activation and recovery time of ICa,L, accelerate the inactivation of ICa,L. IKur has the frequency—dependent characteristics. PIP can partly regain the changed.6. H2O2can inhibit IKur markedly, and make the Ⅰ—Ⅴ curve shifted downward. APO can partly regain the changed.7. H2O2can inhibit Ito markedly, make the Ⅰ—Ⅴ curve shifted downward, slow the activation of Ito, increase the closed—state inactivation of Ito, and have no effects on inactivation and recovery from the inactivation of Ito.. APO can partly regain the changed. |
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