作者
Na Li, Tiannan Wang, Wei Wang, Michael J Cutler, Qiongling Wang, Niels Voigt, David S Rosenbaum, Dobromir Dobrev, Xander HT Wehrens
发表日期
2012/2/3
期刊
Circulation research
卷号
110
期号
3
页码范围
465-470
出版商
Lippincott Williams & Wilkins
简介
Rationale:
Abnormal calcium release from sarcoplasmic reticulum (SR) is considered an important trigger of atrial fibrillation (AF). Whereas increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity has been proposed to contribute to SR leak and AF induction, downstream targets of CaMKII remain controversial.
Objective:
To test the hypothesis that inhibition of CaMKII-phosphorylated type-2 ryanodine receptors (RyR2) prevents AF initiation in FKBP12.6-deficient (−/−) mice.
Methods and Results:
Mice lacking RyR2-stabilizing subunit FKBP12.6 had a higher incidence of spontaneous and pacing-induced AF compared with wild-type mice. Atrial myocytes from FKBP12.6−/− mice exhibited spontaneous Ca2+ waves (SCaWs) leading to Na+/Ca2+-exchanger activation and delayed afterdepolarizations (DADs). Mutation S2814A in RyR2, which inhibits CaMKII phosphorylation, reduced Ca2+ spark …
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N Li, T Wang, W Wang, MJ Cutler, Q Wang, N Voigt… - Circulation research, 2012
