ER stress and calcium-dependent arrhythmias.

ER stress and calcium-dependent arrhythmias.
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DOI:
10.3389/fphys.2022.1041940
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发表时间:
2022
影响因子:
4
通讯作者:
--
中科院分区:
医学2区
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--
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肌浆网 (SR) 作为激活心肌细胞收缩机制的 Ca2+ 的主要来源,在心脏功能中发挥着关键作用。 SR Ca2+通道兰尼碱受体(RyR2)微调的 SR Ca2+ 释放和 SR Ca2+-ATP酶(SERCa2a)对 SR Ca2+ 的再摄取的干扰不仅会损害收缩,还会导致心律失常触发和折返。除了作为主要的 Ca2+ 储存细胞器外,心肌细胞中的 SR 还执行其他细胞类型中内质网 (ER) 的所有功能,包括蛋白质合成、折叠和降解。近年来,内质网应激已被认为是许多心脏病的重要影响因素,包括致命的室性心律失常。因此,这篇简短的综述将重点关注心脏中的 ER 应激机制,以及这些变化如何导致 SR Ca2+ 处理机制中的促心律失常缺陷。
The sarcoplasmic reticulum (SR) plays the key role in cardiac function as the major source of Ca2+ that activates cardiomyocyte contractile machinery. Disturbances in finely-tuned SR Ca2+ release by SR Ca2+ channel ryanodine receptor (RyR2) and SR Ca2+ reuptake by SR Ca2+-ATPase (SERCa2a) not only impair contraction, but also contribute to cardiac arrhythmia trigger and reentry. Besides being the main Ca2+ storage organelle, SR in cardiomyocytes performs all the functions of endoplasmic reticulum (ER) in other cell types including protein synthesis, folding and degradation. In recent years ER stress has become recognized as an important contributing factor in many cardiac pathologies, including deadly ventricular arrhythmias. This brief review will therefore focus on ER stress mechanisms in the heart and how these changes can lead to pro-arrhythmic defects in SR Ca2+ handling machinery.
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