The dual face of connexin-based astroglial Ca(2+) communication: a key player in brain physiology and a prime target in pathology.
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.
Department of Basic Medical Sciences, Physiology group, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.
Marijke
M
De Bock
Department of Basic Medical Sciences, Physiology group, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium. Electronic address: Elke.Decrock@gmail.com.
Elke
E
Decrock
Department of Basic Medical Sciences, Physiology group, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.
Nan
N
Wang
Department of Basic Medical Sciences, Physiology group, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.
Mélissa
M
Bol
Department of Toxicology, Center for Pharmaceutical Research, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, B-1090 Brussels, Belgium.
Mathieu
M
Vinken
Department of Cellular and Molecular Medicine, Laboratory of Molecular and Cellular Signalling, KULeuven, Campus Gasthuisberg O/N-I bus 802, B-3000 Leuven, Belgium.
Geert
G
Bultynck
Department of Basic Medical Sciences, Physiology group, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.
Luc
L
Leybaert
D000255:Adenosine Triphosphate / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002450:Cell Communication; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000378:metabolism / Q000473:pathology
D017630:Connexins; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium
Astrocyte; Ca(2+); Connexin; Intercellular communication; Neuro-glio-vascular unit; Neurodegeneration