The dual face of connexin-based astroglial Ca(2+) communication: a key player in brain physiology and a prime target in pathology

Marijke De Bock, Elke Decrock, Nan Wang, Mélissa Bol, Mathieu Vinken, Geert Bultynck, Luc Leybaert

Research output: Contribution to journalScientific reviewpeer-review


For decades, studies have been focusing on the neuronal abnormalities that accompany neurodegenerative disorders. Yet, glial cells are emerging as important players in numerous neurological diseases. Astrocytes, the main type of glia in the central nervous system , form extensive networks that physically and functionally connect neuronal synapses with cerebral blood vessels. Normal brain functioning strictly depends on highly specialized cellular cross-talk between these different partners to which Ca(2+), as a signaling ion, largely contributes. Altered intracellular Ca(2+) levels are associated with neurodegenerative disorders and play a crucial role in the glial responses to injury. Intracellular Ca(2+) increases in single astrocytes can be propagated toward neighboring cells as intercellular Ca(2+) waves, thereby recruiting a larger group of cells. Intercellular Ca(2+) wave propagation depends on two, parallel, connexin (Cx) channel-based mechanisms: i) the diffusion of inositol 1,4,5-trisphosphate through gap junction channels that directly connect the cytoplasm of neighboring cells, and ii) the release of paracrine messengers such as glutamate and ATP through hemichannels ('half of a gap junction channel'). This review gives an overview of the current knowledge on Cx-mediated Ca(2+) communication among astrocytes as well as between astrocytes and other brain cell types in physiology and pathology, with a focus on the processes of neurodegeneration and reactive gliosis. Research on Cx-mediated astroglial Ca(2+) communication may ultimately shed light on the development of targeted therapies for neurodegenerative disorders in which astrocytes participate. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.

Original languageEnglish
Pages (from-to)2211-2232
Number of pages22
JournalBiochimica et Biophysica Acta
Issue number10
Publication statusPublished - 2014

Bibliographical note

Copyright © 2014 Elsevier B.V. All rights reserved.


  • Adenosine Triphosphate/metabolism
  • Astrocytes/metabolism
  • Brain/metabolism
  • Calcium/metabolism
  • Calcium Signaling
  • Cell Communication
  • Connexins/genetics
  • Gap Junctions/metabolism
  • Gene Expression Regulation
  • Glutamic Acid/metabolism
  • Humans
  • Inositol 1,4,5-Trisphosphate/metabolism
  • Molecular Targeted Therapy
  • Neurodegenerative Diseases/genetics
  • Neurons/metabolism
  • Synapses/metabolism


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