Dysregulated sarcoplasmic reticulum calcium release: potential pharmacological target in cardiac disease.
Dysregulated sarcoplasmic reticulum calcium release: potential pharmacological target in cardiac disease.
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DOI：
10.1016/j.pharmthera.2008.06.002
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发表时间：
2008-09
影响因子：
13.5
通讯作者：
Carnes C
中科院分区：
文献类型：
--
作者：
Györke S;Carnes C
在心脏中，从细胞内Ca 2+储存位点（肌浆网（SR））释放的Ca 2+是心脏收缩力的主要决定因素。SR Ca2+释放由专门的分子机制控制，由心脏ryanodine受体（RyR2）和许多辅助蛋白组成，包括FKBP 12.6、钙螯合蛋白（CASQ2）、三聚蛋白（TRD）和连接蛋白（JN）。获得性和遗传缺陷的释放通道复合物的组件中的结果在频谱的异常Ca2+释放表型，范围从致心律失常的自发Ca2+释放和Ca2+交替的心脏衰竭的收缩期Ca2+释放特征的均匀减少。本文将综述SR和Ca2+释放机制的结构和分子组成，以及SR内Ca2+水平、RyR2s的磷酸化和氧化还原修饰等细胞内因素对SR和Ca2+释放机制的调节，并讨论SR Ca2+释放异常与心律失常、心力衰竭等多种心脏疾病表型的关系，并认为SR Ca 2+释放是潜在的治疗靶点。
In the heart, Ca2+ released from the intracellular Ca2+ storage site, the sarcoplasmic reticulum (SR), is the principal determinant of cardiac contractility. SR Ca2+ release is controlled by dedicated molecular machinery, composed of the cardiac ryanodine receptor (RyR2) and a number of accessory proteins, including FKBP12.6, calsequestrin (CASQ2), triadin (TRD) and junctin (JN). Acquired and genetic defects in the components of the release channel complex result in a spectrum of abnormal Ca2+ release phenotypes ranging from arrhythmogenic spontaneous Ca2+ releases and Ca2+ alternans to the uniformly diminished systolic Ca2+ release characteristic of heart failure. In this article, we will present an overview of the structure and molecular components of the SR and Ca2+ release machinery and its modulation by different intracellular factors, such as Ca2+ levels inside the SR as well as phosphorylation and redox modification of RyR2s.We will also discuss the relationships between abnormal SR Ca2+ release and various cardiac disease phenotypes, including, arrhythmias and heart failure, and consider SR Ca2+ release as a potential therapeutic target.
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影响因子：
4.8
作者：
Aracena-Parks, Paula;Goonasekera, Sanjeewa A.;Hamilton, Susan L.
通讯作者：
Hamilton, Susan L.
DOI：
10.1196/annals.1341.008
发表时间：
2005-01-01
期刊：
COMMUNICATIVE CARDIAC CELL
影响因子：
--
作者：
Bers, DM;Guo, T
通讯作者：
Guo, T
影响因子：
64.5
作者：
BRILLANTES, AMB;ONDRIAS, K;MARKS, AR
通讯作者：
MARKS, AR
影响因子：
5.5
作者：
ALLEN, DG;EISNER, DA;ORCHARD, CH
通讯作者：
ORCHARD, CH
DOI：
10.1152/ajpcell.1997.272.5.c1726
发表时间：
1997-05-01
影响因子：
5.5
作者：
Barg, S;Copello, JA;Fleischer, S
通讯作者：
Fleischer, S