The endoplasmic reticulum (ER) is a morphologically and functionally diverse organelle capable of integrating multiple extracellular and internal signals and generating adaptive cellular responses. It plays fundamental roles in protein synthesis and folding and in cellular responses to metabolic and proteotoxic stress. In addition, the ER stores and releases Ca(2+) in sophisticated scenarios that regulate a range of processes in excitable cells throughout the body, including muscle contraction and relaxation, endocrine regulation of metabolism, learning and memory, and cell death. One or more Ca(2+) ATPases and two types of ER membrane Ca(2+) channels (inositol trisphosphate and ryanodine receptors) are the major proteins involved in ER Ca(2+) uptake and release, respectively. There are also direct and indirect interactions of ER Ca(2+) stores with plasma membrane and mitochondrial Ca(2+)-regulating systems. Pharmacological agents that selectively modify ER Ca(2+) release or uptake have enabled studies that revealed many different physiological roles for ER Ca(2+) signaling. Several inherited diseases are caused by mutations in ER Ca(2+)-regulating proteins, and perturbed ER Ca(2+) homeostasis is implicated in a range of acquired disorders. Preclinical investigations suggest a therapeutic potential for use of agents that target ER Ca(2+) handling systems of excitable cells in disorders ranging from cardiac arrhythmias and skeletal muscle myopathies to Alzheimer disease.

中文翻译：

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内质网 Ca(2+) 在健康和疾病中可兴奋细胞中的处理。

内质网 (ER) 是一种形态和功能多样的细胞器，能够整合多种细胞外和内部信号并产生适应性细胞反应。它在蛋白质合成和折叠以及细胞对代谢和蛋白毒性应激的反应中起着重要作用。此外，内质网在复杂的场景中存储和释放 Ca(2+)，这些场景调节全身可兴奋细胞的一系列过程，包括肌肉收缩和放松、新陈代谢的内分泌调节、学习和记忆以及细胞死亡。一种或多种 Ca(2+) ATPases 和两种类型的 ER 膜 Ca(2+) 通道（三磷酸肌醇和兰尼碱受体）分别是参与 ER Ca(2+) 摄取和释放的主要蛋白质。还有内质网 Ca(2+) 存储与质膜和线粒体 Ca(2+) 调节系统的直接和间接相互作用。有选择地修改 ER Ca(2+) 释放或吸收的药理学试剂已经启用了揭示 ER Ca(2+) 信号传导的许多不同生理作用的研究。几种遗传性疾病是由 ER Ca(2+) 调节蛋白的突变引起的，而扰乱的 ER Ca(2+) 稳态与一系列获得性疾病有关。临床前研究表明，在从心律失常和骨骼肌肌病到阿尔茨海默病的各种疾病中，使用靶向可兴奋细胞的 ER Ca(2+) 处理系统的药剂具有治疗潜力。有选择地修改 ER Ca(2+) 释放或吸收的药理学试剂已经启用了揭示 ER Ca(2+) 信号传导的许多不同生理作用的研究。几种遗传性疾病是由 ER Ca(2+) 调节蛋白的突变引起的，而扰乱的 ER Ca(2+) 稳态与一系列获得性疾病有关。临床前研究表明，在从心律失常和骨骼肌肌病到阿尔茨海默病的各种疾病中，使用靶向可兴奋细胞的 ER Ca(2+) 处理系统的药剂具有治疗潜力。有选择地修改 ER Ca(2+) 释放或吸收的药理学试剂已经启用了揭示 ER Ca(2+) 信号传导的许多不同生理作用的研究。几种遗传性疾病是由 ER Ca(2+) 调节蛋白的突变引起的，而扰乱的 ER Ca(2+) 稳态与一系列获得性疾病有关。临床前研究表明，在从心律失常和骨骼肌肌病到阿尔茨海默病的各种疾病中，使用靶向可兴奋细胞的 ER Ca(2+) 处理系统的药剂具有治疗潜力。