Abstract:
The ryanodine receptor type 2 (RyR) is a key player in Ca2+ handling during excitation-contraction coupling. During each heartbeat, RyR channels are responsible for linking the action potential with the contractile machinery of the cardiomyocyte by releasing Ca2+ from the sarcoplasmic reticulum. RyR function is fine-tuned by associated signalling molecules, arrangement in clusters and subcellular localization. These parameters together define RyR function within microdomains and are subject to disease remodelling. This review describes the latest findings on RyR microdomain organization, the alterations with disease which result in increased subcellular heterogeneity and emergence of microdomains with enhanced arrhythmogenic potential, and presents novel technologies that guide future research to study and target RyR channels within specific microdomains.
摘要:
ryanodine受体2型(RyR)是激发-收缩偶联过程中Ca2处理的关键因素。在每次心跳期间,RyR通道负责通过从肌浆网释放Ca2来将动作电位与心肌细胞的收缩机械连接。RyR功能由相关的信号分子微调,簇排列和亚细胞定位。这些参数一起定义了微结构域内的RyR功能并且经受疾病重塑。这篇综述描述了RyR微域组织的最新发现,疾病的改变导致亚细胞异质性增加和心律失常潜能增强的微域的出现,并提出了指导未来研究的新技术,以研究和靶向特定微域内的RyR通道。