Expanding the store-operated Ca2+ entry microdomain through Ca2+ tunneling

Ca2+ is unique among second messenger in terms of its spatial and temporal breadth. On the spatial level Ca2+ signals extend from nm to cm scales (seven orders of magnitude), and in the temporal dimension it signals in the range of mu sec to hours (nine orders of magnitude). Furthermore, Ca2+ activates with exquisite specificity diverse, often opposing, cellular events. How Ca2+ achieves such a broad spatial and temporal coverage while maintaining signaling specificity is an area of active research with cell type specific nuances. Here, we discuss one modality of Ca2+ signaling that operates downstream of store-operated Ca2+ entry (SOCE), known as Ca2+ tunneling, that expands SOCE signaling while maintaining specificity. We focus on recent findings that argue that Ca2+ tunneling has been adapted for cortical signaling.