title: Prolonged action potential duration in cardiac ablation of PDK1 mice.
abstract: The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University Nanjing, China.
authors.forename: Zhongzhou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Dao W
authors.initials: DW
authors.lastname: Wang
keywords: L-type Ca2+ current; PDK1; action potential duration; patch clamp; transient outward potassium current