Calcium signaling in neuroglia

Int Rev Cell Mol Biol. 2021;362:1-53. doi: 10.1016/bs.ircmb.2021.01.003. Epub 2021 Apr 10.


Glial cells exploit calcium (Ca2+) signals to perceive the information about the activity of the nervous tissue and the tissue environment to translate this information into an array of homeostatic, signaling and defensive reactions. Astrocytes, the best studied glial cells, use several Ca2+ signaling generation pathways that include Ca2+ entry through plasma membrane, release from endoplasmic reticulum (ER) and from mitochondria. Activation of metabotropic receptors on the plasma membrane of glial cells is coupled to an enzymatic cascade in which a second messenger, InsP3 is generated thus activating intracellular Ca2+ release channels in the ER endomembrane. Astrocytes also possess store-operated Ca2+ entry and express several ligand-gated Ca2+ channels. In vivo astrocytes generate heterogeneous Ca2+ signals, which are short and frequent in distal processes, but large and relatively rare in soma. In response to neuronal activity intracellular and inter-cellular astrocytic Ca2+ waves can be produced. Astrocytic Ca2+ signals are involved in secretion, they regulate ion transport across cell membranes, and are contributing to cell morphological plasticity. Therefore, astrocytic Ca2+ signals are linked to fundamental functions of the central nervous system ranging from synaptic transmission to behavior. In oligodendrocytes, Ca2+ signals are generated by plasmalemmal Ca2+ influx, or by release from intracellular stores, or by combination of both. Microglial cells exploit Ca2+ permeable ionotropic purinergic receptors and transient receptor potential channels as well as ER Ca2+ release. In this contribution, basic morphology of glial cells, glial Ca2+ signaling toolkit, intracellular Ca2+ signals and Ca2+-regulated functions are discussed with focus on astrocytes.

Keywords: Astrocytes; Calcium signaling; Calcium signals; Microglia; Oligodendrocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Calcium Signaling*
  • Homeostasis
  • Humans
  • Microglia / metabolism
  • Neuroglia / metabolism*
  • Neuroprotection