Center for Physiology and Pharmacology, Department of Neurophysiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Cell Physiology and Metabolism, University of Geneva, 1201 Geneva, Switzerland.
Cells. 2021 Sep 8;10(9):2356. doi: 10.3390/cells10092356.
Current knowledge on store-operated Ca entry (SOCE) regarding its localization, kinetics, and regulation is mostly derived from studies performed in non-excitable cells. After a long time of relative disinterest in skeletal muscle SOCE, this mechanism is now recognized as an essential contributor to muscle physiology, as highlighted by the muscle pathologies that are associated with mutations in the SOCE molecules STIM1 and Orai1. This review mainly focuses on the peculiar aspects of skeletal muscle SOCE that differentiate it from its counterpart found in non-excitable cells. This includes questions about SOCE localization and the movement of respective proteins in the highly organized skeletal muscle fibers, as well as the diversity of expressed STIM isoforms and their differential expression between muscle fiber types. The emerging evidence of a phasic SOCE, which is activated during EC coupling, and its physiological implication is described as well. The specific issues related to the use of SOCE modulators in skeletal muscles are discussed. This review highlights the complexity of SOCE activation and its regulation in skeletal muscle, with an emphasis on the most recent findings and the aim to reach a current picture of this mesmerizing phenomenon.
目前关于钙库操纵性钙内流（SOCE）的定位、动力学和调控的知识主要来源于非兴奋性细胞的研究。经过很长一段时间对骨骼肌 SOCE 的相对不感兴趣，现在人们认识到这种机制是肌肉生理学的一个重要贡献，这突出表现在与 SOCE 分子 STIM1 和 Orai1 突变相关的肌肉病理学中。本文主要集中讨论了骨骼肌 SOCE 的独特方面，这些方面使其与非兴奋性细胞中的 SOCE 区分开来。这包括关于 SOCE 定位和相应蛋白在高度组织化的骨骼肌纤维中的运动的问题，以及表达的 STIM 同工型的多样性及其在肌纤维类型之间的差异表达。还描述了在 EC 偶联过程中激活的、具有时相性的 SOCE 及其生理意义。讨论了与骨骼肌中使用 SOCE 调节剂相关的具体问题。本文综述强调了 SOCE 在骨骼肌中的激活和调节的复杂性，重点介绍了最新的发现，并旨在描绘这个迷人现象的最新全貌。
