CaMKII-Dependent Diastolic SR Ca2+ Leak and Elevated Diastolic Ca2+ Levels in Right Atrial Myocardium of Patients With Atrial Fibrillation
CaMKII-Dependent Diastolic SR Ca2+ Leak and Elevated Diastolic Ca2+ Levels in Right Atrial Myocardium of Patients With Atrial Fibrillation
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DOI：
10.1161/circresaha.109.203836
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发表时间：
2010-04-02
影响因子：
20.1
通讯作者：
Maier, Lars S.
中科院分区：
文献类型：
--
作者：
Neef, Stefan;Dybkova, Nataliya;Maier, Lars S.
基本原理：虽然研究表明，舒张期Ca 2+水平可能会增加心房颤动（AF），这一假设从未得到验证。肌浆网（SR）舒张期Ca ~（2+）漏出可能增加舒张期Ca ~（2+）水平，通过Na ~+/Ca ~（2+）交换的瞬时内向电流触发或维持AF。在心室肌中，钙/钙调蛋白依赖性蛋白激酶（CaMK）II引起的Ryanodine受体2型（RyR 2）磷酸化是SR Ca 2+渗漏的重要机制。目的：我们检验了房颤患者心房肌中CaMK II依赖性舒张期SR Ca 2+渗漏和舒张期Ca 2+水平升高的假设。我们使用房颤患者与窦性心律患者的分离的人右心房肌细胞，发现CaMK II表达增加40 +/- 14%（P
Rationale: Although research suggests that diastolic Ca2+ levels might be increased in atrial fibrillation (AF), this hypothesis has never been tested. Diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) might increase diastolic Ca2+ levels and play a role in triggering or maintaining AF by transient inward currents through Na+/Ca2+ exchange. In ventricular myocardium, ryanodine receptor type 2 (RyR2) phosphorylation by Ca2+/calmodulin-dependent protein kinase (CaMK)II is emerging as an important mechanism for SR Ca2+ leak.Objective: We tested the hypothesis that CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels occurs in atrial myocardium of patients with AF.Methods and Results: We used isolated human right atrial myocytes from patients with AF versus sinus rhythm and found CaMKII expression to be increased by 40 +/- 14% (P