1Faculty of Life Sciences, The University of Manchester, Manchester, M13 9PT, UK
2Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain; and Department of Neurosciences, University of the Basque Country UPV/EHU, 48940, Leioa, Spain
3Department of Neurobiology, Center for Glial Biology in Medicine, Atomic Force Microscopy & Nanotechnology Laboratories, Civitan International Research Center, Evelyn F. McKnight Brain Institute, University of Alabama, Birmingham, AL 35294, USA
4Department of Biotechnology, University or Rijeka, 51000 Rijeka, Croatia

Abstract 

Neuroglial cells are homeostatic neural cells. Generally, they are electrically non-excitable and their activation is associated with the generation of complex intracellular Ca2+ signals that define the “Ca2+ excitability” of glia. In mammalian glial cells the major source of Ca2+ for this excitability is the lumen of the endoplasmic reticulum (ER), which is ultimately (re)filled from the extracellular space. This occurs via store-operated Ca2+ entry (SoCE) which is supported by a specific signaling system connecting the ER with plasmalemmal Ca2+ entry. Here, emptying of the ER Ca2+ store is necessary and sufficient for the activation of SOCE, and without Ca2+ influx via SOCE the ER store cannot be refilled. The molecular arrangements underlying SOCE are relatively complex and include plasmalemmal channels, ER Ca2+ sensors, such as stromal interaction molecule, and possibly ER Ca2+ pumps (of the SERCA type). There are at least two sets of plasmalemmal channels mediating SOCE, the Ca2+-release activated channels, Orai, and transient receptor potential (TRP) channels. The molecular identity of neuroglial SOCE has not been yet identified unequivocally. However, it seems that Orai is predominantly expressed in microglia, whereas astrocytes and oligodendrocytes rely more on TRP channels to produce SoCE. in physiological conditions the SoCE pathway is instrumental for the sustained phase of the Ca2+ signal observed following stimulation of metabotropic receptors on glial cells.

Keywords

calcium signaling; astrocyte; oligodendrocyte; microglia; store-operated calcium entry; TRP; STIM; orai

[SpringerLink]