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Annual Review of Physiology

Volume 87, 2025

Store-Operated Calcium Channels in the Nervous System

  • Kirill S. Korshunov1 and Murali Prakriya1
  • Department of Pharmacology, Northwestern Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; email: [email protected]
  • Vol. 87:173-199 (Volume publication date February 2025)
  • First published as a Review in Advance on November 25, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

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.

Keyword(s): astrocytes, Ca2+, microglia, neurons, Orai1, SOCE, STIM1, store-operated calcium entry
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2025-02-10
2025-06-15
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Store-Operated Calcium Channels in the Nervous System
Annual Review of Physiology 87, 173 (2025); https://doi.org/10.1146/annurev-physiol-022724-105330
/content/journals/10.1146/annurev-physiol-022724-105330
/content/journals/10.1146/annurev-physiol-022724-105330
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