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Int. J. Mol. Sci. 2017, 18(4), 688;

Oxidative Stress-Induced Afterdepolarizations and Protein Kinase C Signaling

Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Department of Biochemistry and Molecular Biology, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editors: Yi-Han Chen and Jianmin Cui
Received: 1 February 2017 / Revised: 6 March 2017 / Accepted: 14 March 2017 / Published: 30 March 2017
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: oxidative stress; afterdepolarization; triggered activity; protein kinase C; arrhythmia oxidative stress; afterdepolarization; triggered activity; protein kinase C; arrhythmia

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Fei, Y.-D.; Li, W.; Hou, J.-W.; Guo, K.; Chen, X.-M.; Chen, Y.-H.; Wang, Q.; Xu, X.-L.; Wang, Y.-P.; Li, Y.-G. Oxidative Stress-Induced Afterdepolarizations and Protein Kinase C Signaling. Int. J. Mol. Sci. 2017, 18, 688.

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