Abstract
Store-operated calcium channels (SOCs) are widely expressed in excitatory and non-excitatory cells where they mediate significant store-operated calcium entry (SOCE), an important pathway for calcium signaling throughout the body. While the activity of SOCs has been well studied in non-excitable cells, attention has turned to their role in neurons and glia in recent years. In particular, the role of SOCs in the nervous system has been extensively investigated, with links to their dysregulation found in a wide variety of neurological diseases from Alzheimer’s disease (AD) to pain. In this review, we provide an overview of their molecular components, expression, and physiological role in the nervous system and describe how the dysregulation of those roles could potentially lead to various neurological disorders. Although further studies are still needed to understand how SOCs are activated under physiological conditions and how they are linked to pathological states, growing evidence indicates that SOCs are important players in neurological disorders and could be potential new targets for therapies. While the role of SOCE in the nervous system continues to be multifaceted and controversial, the study of SOCs provides a potentially fruitful avenue into better understanding the nervous system and its pathologies.
Highlights
Store-operated calcium channels (SOCs) are calcium-selective cation channels that represent a major pathway for calcium signaling throughout the body
Store-operated calcium channels are functional throughout the nervous system and regulate a wide variety of physiological processes (Table 1)
While STIMs and Orais have been shown to have significant expression in many regions of the nervous system, interestingly their expression levels and distribution patterns vary during developmental phases and in different regions of the nervous system
Summary
Store-operated calcium channels (SOCs) are calcium-selective cation channels that represent a major pathway for calcium signaling throughout the body. We summarize the current understanding of the physiological role of SOCs in the nervous system by outlining their expression, molecular components, and functions in neurons from different brain regions and glial cells. Both STIM proteins are involved in calcium homeostasis in cortical neurons, STIM1 mainly activates SOCE, whereas STIM2 regulates resting Ca2+ levels (Gruszczynska-Biegala and Kuznicki, 2013).
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