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Updated: Jun 20, 2026

Whole-Cell Recording of Calcium Release-Activated Calcium (CRAC) Currents in Human T Lymphocytes
Published on: December 21, 2010
B-lymphocyte calcium influx
Leslie B King1, Bruce D Freedman
1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Insights
Calcium signaling in B lymphocytes is finely tuned by store-operated calcium release-activated calcium (CRAC) channels and innate stimuli. This review explores regulatory mechanisms and cross-talk for immune cell function.
Area of Science:
- Immunology
- Cellular Physiology
- Molecular Biology
Background:
- Cytoplasmic calcium concentration dynamics are crucial for lymphocyte immune cell function.
- Key components of store-operated calcium entry, including calcium release-activated calcium (CRAC) channels and STIM1, have been identified.
- Fine regulation of CRAC channel activation in inflammatory environments remains underexplored.
Purpose of the Study:
- To review underexplored aspects of store-operated and store-independent calcium signaling in B lymphocytes.
- To discuss regulatory mechanisms of CRAC channel activation and sustained calcium entry.
- To explore innate calcium signaling pathways in B cells and their cross-regulation with CRAC channels.
Main Methods:
- Review of existing literature on calcium signaling in B lymphocytes.
- Discussion of proposed mechanisms for CRAC channel regulation and activation.
- Analysis of the interplay between innate stimuli-activated calcium channels and CRAC channels.
Main Results:
- Evidence suggests regulated coupling between endoplasmic reticulum (ER) stores and CRAC channels for fine-tuning activation.
- Mechanisms sustaining the duration of calcium entry via CRAC channels are discussed.
- Distinct calcium-permeant non-selective cation channels (NSCCs) activated by innate stimuli in B cells are examined.
Conclusions:
- Fine-tuning of CRAC channel activation and sustained calcium entry are critical for B lymphocyte function.
- Innate calcium signaling pathways in B cells exist and cross-regulate with CRAC channels.
- Understanding these complex calcium signaling networks is essential for deciphering B cell immunology.
Abstract:
Dynamic changes in cytoplasmic calcium concentration dictate the immunological fate and functions of lymphocytes. During the past few years, important details have been revealed about the mechanism of store-operated calcium entry in lymphocytes, including the molecular identity of calcium release-activated calcium (CRAC) channels and the endoplasmic reticulum (ER) calcium sensor (STIM1) responsible for CRAC channel activation following calcium depletion of stores. However, details of the potential fine regulation of CRAC channel activation that may be imposed on lymphocytes following physiologic stimulation within an inflammatory environment have not been fully addressed. In this review, we discuss several underexplored aspects of store-operated (CRAC-mediated) and store-independent calcium signaling in B lymphocytes. First, we discuss results suggesting that coupling between stores and CRAC channels may be regulated, allowing for fine tuning of CRAC channel activation following depletion of ER stores. Second, we discuss mechanisms that sustain the duration of calcium entry via CRAC channels. Finally, we discuss distinct calcium permeant non-selective cation channels (NSCCs) that are activated by innate stimuli in B cells, the potential means by which these innate calcium signaling pathways and CRAC channels crossregulate one another, and the mechanistic basis and physiologic consequences of innate calcium signaling.
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