Korshunov Kirill S, Prakriya Murali
Department of Pharmacology, Northwestern Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; email:
Annu Rev Physiol. 2025 Feb;87(1):173-199. doi: 10.1146/annurev-physiol-022724-105330. Epub 2025 Feb 3.
Store-operated Ca2+ entry (SOCE) is a widespread mechanism of cellular Ca2+ signaling that arises from Ca2+ influx across the plasma membrane through the Orai family of calcium channels in response to depletion of intracellular Ca2+ stores. Orai channels are a crucial Ca2+ entry mechanism in both neurons and glia and are activated by a unique inside-out gating process involving interactions with the endoplasmic reticulum Ca2+ sensors, STIM1 and STIM2. Recent evidence indicates that SOCE is broadly found across all areas of the nervous system where its physiology and pathophysiology is only now beginning to be understood. Here, we review the growing literature on the mechanisms of SOCE in the nervous system and contributions to gene expression, neuronal excitability, synaptic plasticity, and behavior. We also explore the burgeoning links between SOCE and neurological disease and discuss therapeutic implications of targeting SOCE for brain disorders.
储存式钙离子内流（SOCE）是一种广泛存在的细胞钙离子信号传导机制，它是由于细胞内钙离子储存耗尽时，钙离子通过Orai家族钙通道穿过质膜流入细胞而产生的。Orai通道是神经元和神经胶质细胞中一种关键的钙离子内流机制，通过一种独特的由内向外的门控过程被激活，该过程涉及与内质网钙离子传感器STIM1和STIM2的相互作用。最近的证据表明，SOCE广泛存在于神经系统的所有区域，其生理学和病理生理学目前才刚刚开始被理解。在这里，我们综述了关于神经系统中SOCE机制及其对基因表达、神经元兴奋性、突触可塑性和行为的影响的不断增加的文献。我们还探讨了SOCE与神经疾病之间新兴的联系，并讨论了针对SOCE治疗脑部疾病的潜在意义。
