Glial Communication via Gap Junction in Neuroinflammation
Gap junction is the major intercellular channel that facilitates direct signaling between cytoplasmic compartments of adjacent cells by transferring various small molecules (~1,000 Da) and ions. Gap junction consists of a pair of hemichannels, each of which is a hexameric cluster of protein subunits named connexin. Recent studies have revealed that uncoupled “free” hemichannels also facilitate two-way transfer of molecules between the cytosol and extracellular space. In the central nervous system (CNS), gap junctions and hemichannels form the neuron–glia network and contribute to the maintenance of homeostasis by propagating signals and buffering against toxins. Other evidence suggests that gap junctions and hemichannels—especially in glial cells—are also involved in the initiation and amplification of neuroinflammation in various neurological disorders. The purpose of this review is to summarize recent insights into the roles of gap junctions and hemichannels in the physiologic and pathologic conditions of the CNS.
KeywordsPermeability Migration Ischemia Glutathione Hexagonal
This work was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO); grants from the Ministry of Health, Labour and Welfare of Japan; a grant-in-aid for Scientific Research on Innovative Areas; and a grant-in-aid for the Global Center of Excellence Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Conflicts of interest The author has no conflicts of interest to declare.
- Al-Ubaidi MR, White TW, Ripps H, Poras I, Avner P, Gomes D et al (2000) Functional properties, developmental regulation, and chromosomal localization of murine connexin36, a gap-junctional protein expressed preferentially in retina and brain. J Neurosci Res 59(6):813–826, Epub 2000/03/04PubMedGoogle Scholar
- Barbe MT, Monyer H, Bruzzone R (2006) Cell-cell communication beyond connexins: the pannexin channels. Physiology (Bethesda) 21:103–114, Epub 2006/03/28Google Scholar
- Eugenin EA, Eckardt D, Theis M, Willecke K, Bennett MV, Saez JC (2001) Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. Proc Natl Acad Sci U S A 98(7):4190–4195, Epub 2001/03/22PubMedGoogle Scholar
- Masaki K, Suzuki SO, Matsushita T, Yonekawa T, Matsuoka T, Isobe N et al (2012) Extensive loss of connexins in Balo’s disease: evidence for an auto-antibody-independent astrocytopathy via impaired astrocyte-oligodendrocyte/myelin interaction. Acta Neuropathol 123(6):887–900, Epub 2012/03/23PubMedGoogle Scholar
- Menichella DM, Majdan M, Awatramani R, Goodenough DA, Sirkowski E, Scherer SS et al (2006) Genetic and physiological evidence that oligodendrocyte gap junctions contribute to spatial buffering of potassium released during neuronal activity. J Neurosci 26(43):10984–10991, Epub 2006/10/27PubMedGoogle Scholar
- Odermatt B, Wellershaus K, Wallraff A, Seifert G, Degen J, Euwens C et al (2003) Connexin 47 (Cx47)-deficient mice with enhanced green fluorescent protein reporter gene reveal predominant oligodendrocytic expression of Cx47 and display vacuolized myelin in the CNS. J Neurosci 23(11):4549–4559, Epub 2003/06/14PubMedGoogle Scholar
- Takeuchi H (2010) Neurotoxicity by microglia: mechanisms and potential therapeutic strategy. Clin Exp Neuroimmunol 1(1):12–21Google Scholar