Store-operated calcium entry in neuroglia

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.