title: Oxidative Stress-Induced Afterdepolarizations and Protein Kinase C Signaling.
abstract: 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,Land INa,L. These results provide evidence of a link between oxidative stress, PKC activation and afterdepolarizations.
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. fyd6254@gmail.com.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Fei
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. lwcbss@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. houjianwena@126.com.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Hou
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. guokai0201@aliyun.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. chenxmcorrine@outlook.com.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. cyh1726@163.com.
authors.forename: Yi-He
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. wangq0327@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. xu.xiaolei@mayo.edu.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. ypwang555@aliyun.com.
authors.forename: Yue-Peng
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. drliyigang@outlook.com.
authors.forename: Yi-Gang
authors.initials: YG
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction
chemical_list: D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C
keywords: afterdepolarization; arrhythmia; oxidative stress; protein kinase C; triggered activity