Ryanodine receptor as a new therapeutic target of heart failure, and lethal arrhythmia
Ryanodine receptor as a new therapeutic target of heart failure, and lethal arrhythmia
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DOI：
10.1253/circj.cj-08-0070
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发表时间：
2008-04-01
影响因子：
3.3
通讯作者：
Yano, Masafumi
中科院分区：
文献类型：
--
作者：
Yano, Masafumi
肌浆网(SR)对细胞内钙的异常处理是心力衰竭(HF)发生发展的关键因素。不仅钙摄取减少，而且钙的不协调释放在收缩和松弛功能障碍中起着重要作用。心脏舒张期通过兰尼定受体(RyR)2(RyR)2自发释放钙离子，导致肌浆网钙离子含量下降，并触发作为致死性心律失常底物的延迟后除极。儿茶酚胺能多形性室性心动过速(CPVT)或致心律失常性右室心肌病2型(ARVC2)患者的RyR基因突变已有报道。这些突变位点的独特分布导致了这样的概念，即RyR内假定的调节域之间的相互作用可能在调节通道开放方面发挥关键作用，并且在HF和CPVT/ARVC2的通道紊乱中似乎存在共同的异常。从病理条件获得的最新知识可能会导致开发一种新的治疗策略来治疗心力衰竭或心律失常。
Abnormal intracellular Ca2+ handling by the sarcoplasmic reticulum (SR) is a critical factor in the development of heart failure (HF). Not only decreased Ca2+ Uptake, but also uncoordinated Ca2+ release plays a significant role in contractile and relaxation dysfunction. Spontaneous Ca2+ release through ryanodine receptor (RyR) 2, a huge tetrameric protein, during diastole leads to a decrease in the SR Ca2+ content, and also triggers delayed after depolarization that is a substrate for lethal arrhythmia. Several disease-linked mutations of RyR have been reported in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) or arrhythmogenic right ventricular cardiomyopathy type 2 (ARVC2). The unique distribution of these mutation sites has lead to the concept that an interaction among the putative regulatory domains within RyR may play a key role in regulating channel opening, and that there seems to be a common abnormality in the channel disorder of HF and CPVT/ARVC2. Recent knowledge gained from pathological conditions may lead to the development of a new therapeutic strategy for the treatment of HF or cardiac arrhythmia.