CaMKII-dependent phosphorylation of RyR2 promotes targetable pathological RyR2 conformational shift
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- 作者：Hitoshi Uchinoumia ; 1 ; Yi Yanga ; 1 ; Tetsuro Odaa ; b ; Na Lid ; e ; Katherina M. Alsinad ; e ; h ; Jose L. Puglisia ; Ye Chen-Izua ; Razvan L. Corneac ; Xander H.T. Wehrensd ; e ; f ; g ; Donald M. Bersa ; dmbers@ucdavis.edu" class="auth_mail" title="E-mail the corresponding author
- 关键词：AIP ; autocamtide-2 related inhibitory peptide ; Bmax ; binding maximum ; CaM ; calmodulin ; CaMKII ; calcium/calmodulin-dependent protein kinase II ; CaSpF ; calcium spark frequency ; CPVT ; catecholaminergic polymorphic ventricular tachycardia ; DAN ; dantrolene ; F ; fluorescent ; FKBP ; FK506-binding protein ; FRET ; fluorescence resonance energy transfer ; HF ; heart failure ; PKA ; protein kinase A ; ROS ; reactive oxygen species ; RyR1 ; skeletal ryanodine receptor ; RyR2 ; cardiac ryanodine receptor ; SR ; sarcoplasmi
- 刊名：Journal of Molecular and Cellular Cardiology
- 出版年：2016
- 出版时间：September 2016
- 年：2016
- 卷：98
- 期：Complete
- 页码：62-72
- 全文大小：2472 K
文摘
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CaMKII-dependent RyR2 phosphorylation reduces CaM affinity and causes SR Leak.
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RyR2 phosphorylation by CaMKII induces a pathological (unzipped) conformation.
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Dantrolene restores CaM binding affinity and quiets diastolic SR Ca leak.
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Dantrolene & CaM shift pathological conformation back to physiological (normal).
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A common RyR2 pathological state may occur in heart failure, ROS, and CaMKII.