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Sci. STKE, 27 July 2004
Vol. 2004, Issue 243, p. pe34
[DOI: 10.1126/stke.2432004pe34]


Store-Operated Channels: Diversity and Activation Mechanisms

Victoria M. Bolotina*

Boston University School of Medicine, 650 Albany Street, X-704, Boston, MA 02118, USA.

Abstract: This perspective addresses two questions: How many store-operated channels (SOCs) are there, and how many mechanisms can account for SOC activation by depleted stores? Accumulating evidence suggests that the SOC family is not limited to the calcium-selective SOC that is responsible for ICRAC (Ca2+-SOC), but includes poorly selective cation SOCs (cat-SOCs) that may satisfy physiological needs in diverse excitable and nonexcitable cells. A growing number of studies in different cell types support the idea that all the members of SOC family (Ca2+-SOC and cat-SOC) may be activated by depletion of the stores through the same mechanism, which is mediated by calcium influx factor (CIF) and calcium-independent phospholipase A2 (iPLA2). A conformational coupling model is also discussed. To account for the most recent findings, we propose that two distinct classes of calcium-conducting channels may exist in plasma membrane, which respond to different signals: SOCs, which are activated by depletion of calcium stores through the CIF-iPLA2 mechanism [no inositol triphosphate (IP3) needed]; and IP3 receptor–operated channels (IP3ROCs), which are activated by IP3 receptor through a direct coupling mechanism (no store depletion is needed). This model, with two separate mechanisms linked to different channels, may resolve many conflicting findings and interpretations and may give a new perspective on the diversity of calcium influx pathways.

*Corresponding author. E-mail: bolotina{at}

Citation: V. M. Bolotina, Store-Operated Channels: Diversity and Activation Mechanisms. Sci. STKE 2004, pe34 (2004).

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