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Updated: Jun 8, 2026

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels
Youjun Wang1, Xiaoxiang Deng, Salvatore Mancarella
1Department of Biochemistry and Cardiovascular Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
Abstract:
Calcium signals, pivotal in controlling cell function, can be generated by calcium entry channels activated by plasma membrane depolarization or depletion of internal calcium stores. We reveal a regulatory link between these two channel subtypes mediated by the ubiquitous calcium-sensing STIM proteins. STIM1 activation by store depletion or mutational modification strongly suppresses voltage-operated calcium (Ca(V)1.2) channels while activating store-operated Orai channels. Both actions are mediated by the short STIM-Orai activating region (SOAR) of STIM1. STIM1 interacts with Ca(V)1.2 channels and localizes within discrete endoplasmic reticulum/plasma membrane junctions containing both Ca(V)1.2 and Orai1 channels. Hence, STIM1 interacts with and reciprocally controls two major calcium channels hitherto thought to operate independently. Such coordinated control of the widely expressed Ca(V)1.2 and Orai channels has major implications for Ca(2+) signal generation in excitable and nonexcitable cells.
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