Oxidative Stress-Induced Afterdepolarizations and Protein Kinase C Signaling.
Oxidative Stress-Induced Afterdepolarizations and Protein Kinase C Signaling.
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氧化应激诱导的后去极化和蛋白激酶 C 信号转导
DOI：
10.3390/ijms18040688
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发表时间：
2017-03-30
影响因子：
5.6
通讯作者：
Li YG
中科院分区：
文献类型：
--
作者：
Fei YD;Li W;Hou JW;Guo K;Chen XM;Chen YH;Wang Q;Xu XL;Wang YP;Li YG
背景：过氧化氢（H2O2）诱导的氧化应激已被证明可诱导分离的肌细胞后去极化并触发活性，但其潜在机制尚不完全清楚。我们的目的是探讨蛋白激酶C （PKC）激活是否在氧化应激诱导的后去极化中起重要作用。方法：采用膜片钳技术记录离体兔心肌细胞的动作电位和离子电流。采用H2O2 （1 mM）灌注诱导氧化应激，并采用PKC特异性经典抑制剂Gö 6983 （1 μM）检测PKC的参与情况。结果：H2O2灌注延长动作电位持续时间，诱导后去极化。Gö 6983预处理可以防止h2o2诱导的后去极化的出现。添加H2O2 Gö 6983可有效抑制H2O2诱导的后去极化。H2O2增加了后期钠电流（INa，L） （n = 7, p < 0.01）和L型钙电流（ICa，L） （n = 5, p < 0.01）， Gö 6983对两者有显著的逆转作用（p < 0.01）。H2O2增加了瞬时外向钾电流（Ito） （n = 6, p < 0.05）。而Gö 6983对h2o2诱导的Ito增强作用不大。结论：H2O2通过激活PKC和增强ICa，L和INa，L诱导后去极化。这些结果提供了氧化应激、PKC激活和后去极化之间联系的证据。
Background: Hydrogen peroxide (H2O2)-induced oxidative stress has been demonstrated to induce afterdepolarizations and triggered activities in isolated myocytes, but the underlying mechanisms remain not fully understood. We aimed to explore whether protein kinase C (PKC) activation plays an important role in oxidative stress-induced afterdepolarizations. Methods: Action potentials and ion currents of isolated rabbit cardiomyocytes were recorded using the patch clamp technique. H2O2 (1 mM) was perfused to induce oxidative stress and the specific classical PKC inhibitor, Gö 6983 (1 μM), was applied to test the involvement of PKC. Results: H2O2 perfusion prolonged the action potential duration and induced afterdepolarizations. Pretreatment with Gö 6983 prevented the emergence of H2O2-induced afterdepolarizations. Additional application of Gö 6983 with H2O2 effectively suppressed H2O2-induced afterdepolarizations. H2O2 increased the late sodium current (INa,L) (n = 7, p < 0.01) and the L-type calcium current (ICa,L) (n = 5, p < 0.01), which were significantly reversed by Gö 6983 (p < 0.01). H2O2 also increased the transient outward potassium current (Ito) (n = 6, p < 0.05). However, Gö 6983 showed little effect on H2O2-induced enhancement of Ito. Conclusions: H2O2 induced afterdepolarizations via the activation of PKC and the enhancement of ICa,L and INa,L. These results provide evidence of a link between oxidative stress, PKC activation and afterdepolarizations.
影响因子：
5.5
作者：
Xing, Dezhi;Chaudhary, Ashok K.;Miller, Francis J., Jr.;Martins, James B.
通讯作者：
Martins, James B.