RyR2磷酸化在心力衰竭中的作用

The role of RyR2 phosphorylation in heart failure

心力衰竭在细胞水平主要表现为心肌以兴奋-收缩耦联(excitement-contraction coupling,ECC)为基础的收缩功能障碍,而Ca2+信号转导在此过程中起着非常重要的作用。肌浆网(sarcoplasmic reticulum,SR)兰尼碱受体(ryanodine receptor type 2,RyR2)是心肌最重要的钙释放通道,RyR2磷酸化是肌浆网钙释放的基础,而RyR2磷酸化主要受蛋白激酶A(protein kinase A,PKA)和钙离子/钙调蛋白依赖性蛋白激酶Ⅱ(calcium/calmodulin dependent protein kinaseⅡ,CaMKⅡ)的调控。目前对RyR2磷酸化的研究已经非常广泛,但对其涉及心力衰竭的具体发病机制仍有争议,本综述主要针此问题进行阐述。

Heart failure is mainly characterized by myocardial systolic dysfunction ,which is based on excitement-contraction coupling on the cellular level, and calcium （Ca2＋） signaling plays a very important role in this process. The ryanodine receptor （RyR）/calcium release channel on the sarcoplasmic reticulum （SR） is the major Ca2＋ source of required for cardiac muscle excitation- contraction coupling. RyR2 phosphorylation is the basis of SR calcium release, and RyR2 phosphorylation is mainly controled by protein kinase A （PKA） and calcium/calmodulin dependent protein kinase II（CaMK II）, Although widely research in this area, excessive activation of RyR2 phosphorylation involved in the pathogenesis of heart failure are still controversial, which is discussed in this review.