Glial Communication via Gap Junction in Neuroinflammation

  • Hideyuki Takeuchi
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 7)


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.


Amyotrophic Lateral Sclerosis Experimental Autoimmune Encephalomyelitis Glycyrrhetinic Acid Connexin Gene Connexin Channel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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.


  1. Allen K, Fuchs EC, Jaschonek H, Bannerman DM, Monyer H (2011) Gap junctions between interneurons are required for normal spatial coding in the hippocampus and short-term spatial memory. J Neurosci 31(17):6542–6552, Epub 2011/04/29PubMedGoogle Scholar
  2. Altevogt BM, Paul DL (2004) Four classes of intercellular channels between glial cells in the CNS. J Neurosci 24(18):4313–4323, Epub 2004/05/07PubMedGoogle Scholar
  3. Altevogt BM, Kleopa KA, Postma FR, Scherer SS, Paul DL (2002) Connexin29 is uniquely distributed within myelinating glial cells of the central and peripheral nervous systems. J Neurosci 22(15):6458–6470, Epub 2002/08/02PubMedGoogle Scholar
  4. 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
  5. Alvarez-Maubecin V, Garcia-Hernandez F, Williams JT, Van Bockstaele EJ (2000) Functional coupling between neurons and glia. J Neurosci 20(11):4091–4098, Epub 2000/05/20PubMedGoogle Scholar
  6. Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32(1):1–14, Epub 2000/09/07PubMedGoogle Scholar
  7. Anzini P, Neuberg DH, Schachner M, Nelles E, Willecke K, Zielasek J et al (1997) Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32. J Neurosci 17(12):4545–4551, Epub 1997/06/15PubMedGoogle Scholar
  8. Bani-Yaghoub M, Bechberger JF, Underhill TM, Naus CC (1999a) The effects of gap junction blockage on neuronal differentiation of human NTera2/clone D1 cells. Exp Neurol 156(1):16–32, Epub 1999/04/08PubMedGoogle Scholar
  9. Bani-Yaghoub M, Underhill TM, Naus CC (1999b) Gap junction blockage interferes with neuronal and astroglial differentiation of mouse P19 embryonal carcinoma cells. Dev Genet 24(1–2):69–81, Epub 1999/03/18PubMedGoogle Scholar
  10. 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
  11. Bittman KS, LoTurco JJ (1999) Differential regulation of connexin 26 and 43 in murine neocortical precursors. Cereb Cortex 9(2):188–195, Epub 1999/04/29PubMedGoogle Scholar
  12. Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8(1):57–69, Epub 2006/12/21PubMedGoogle Scholar
  13. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G et al (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312(5778):1389–1392, Epub 2006/06/03PubMedGoogle Scholar
  14. Bouskila Y, Dudek FE (1993) Neuronal synchronization without calcium-dependent synaptic transmission in the hypothalamus. Proc Natl Acad Sci U S A 90(8):3207–3210, Epub 1993/04/15PubMedGoogle Scholar
  15. Brand-Schieber E, Werner P, Iacobas DA, Iacobas S, Beelitz M, Lowery SL et al (2005) Connexin43, the major gap junction protein of astrocytes, is down-regulated in inflamed white matter in an animal model of multiple sclerosis. J Neurosci Res 80(6):798–808, Epub 2005/05/18PubMedGoogle Scholar
  16. Bukauskas FF, Jordan K, Bukauskiene A, Bennett MV, Lampe PD, Laird DW et al (2000) Clustering of connexin 43-enhanced green fluorescent protein gap junction channels and functional coupling in living cells. Proc Natl Acad Sci U S A 97(6):2556–2561, Epub 2000/03/08PubMedGoogle Scholar
  17. Chang Q, Gonzalez M, Pinter MJ, Balice-Gordon RJ (1999) Gap junctional coupling and patterns of connexin expression among neonatal rat lumbar spinal motor neurons. J Neurosci 19(24):10813–10828, Epub 1999/12/14PubMedGoogle Scholar
  18. Charles A (1998) Intercellular calcium waves in glia. Glia 24(1):39–49, Epub 1998/08/13PubMedGoogle Scholar
  19. Christie MJ, Williams JT, North RA (1989) Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats. J Neurosci 9(10):3584–3589, Epub 1989/10/01PubMedGoogle Scholar
  20. Contreras JE, Saez JC, Bukauskas FF, Bennett MV (2003) Gating and regulation of connexin 43 (Cx43) hemichannels. Proc Natl Acad Sci U S A 100(20):11388–11393, Epub 2003/09/18PubMedGoogle Scholar
  21. Dahl G, Locovei S (2006) Pannexin: to gap or not to gap, is that a question? IUBMB Life 58(7):409–419, Epub 2006/06/28PubMedGoogle Scholar
  22. de Pina-Benabou MH, Szostak V, Kyrozis A, Rempe D, Uziel D, Urban-Maldonado M et al (2005) Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia. Stroke 36(10):2232–2237, Epub 2005/09/24PubMedGoogle Scholar
  23. De Vuyst E, Decrock E, De Bock M, Yamasaki H, Naus CC, Evans WH et al (2007) Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor. Mol Biol Cell 18(1):34–46, Epub 2006/11/03PubMedGoogle Scholar
  24. Deans MR, Gibson JR, Sellitto C, Connors BW, Paul DL (2001) Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36. Neuron 31(3):477–485, Epub 2001/08/23PubMedGoogle Scholar
  25. Dermietzel R, Traub O, Hwang TK, Beyer E, Bennett MV, Spray DC et al (1989) Differential expression of three gap junction proteins in developing and mature brain tissues. Proc Natl Acad Sci U S A 86(24):10148–10152, Epub 1989/12/01PubMedGoogle Scholar
  26. Dermietzel R, Hertberg EL, Kessler JA, Spray DC (1991) Gap junctions between cultured astrocytes: immunocytochemical, molecular, and electrophysiological analysis. J Neurosci 11(5):1421–1432, Epub 1991/05/01PubMedGoogle Scholar
  27. Dermietzel R, Gao Y, Scemes E, Vieira D, Urban M, Kremer M et al (2000) Connexin43 null mice reveal that astrocytes express multiple connexins. Brain Res Brain Res Rev 32(1):45–56, Epub 2000/04/07PubMedGoogle Scholar
  28. 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
  29. Eugenin EA, Basilio D, Saez JC, Orellana JA, Raine CS, Bukauskas F et al (2012) The role of gap junction channels during physiologic and pathologic conditions of the human central nervous system. J Neuroimmune Pharmacol 7(3):499–518, Epub 2012/03/23PubMedGoogle Scholar
  30. Flagg-Newton J, Simpson I, Loewenstein WR (1979) Permeability of the cell-to-cell membrane channels in mammalian cell junction. Science 205(4404):404–407, Epub 1979/07/27PubMedGoogle Scholar
  31. Flower NE (1977) Invertebrate gap junctions. J Cell Sci 25:163–171, Epub 1977/06/01PubMedGoogle Scholar
  32. Frank M, Eiberger B, Janssen-Bienhold U, de Sevilla Muller LP, Tjarks A, Kim JS et al (2010) Neuronal connexin-36 can functionally replace connexin-45 in mouse retina but not in the developing heart. J Cell Sci 123(Pt 20):3605–3615, Epub 2010/10/12PubMedGoogle Scholar
  33. Frantseva MV, Kokarovtseva L, Perez Velazquez JL (2002) Ischemia-induced brain damage depends on specific gap-junctional coupling. J Cereb Blood Flow Metab 22(4):453–462, Epub 2002/03/29PubMedGoogle Scholar
  34. Fushiki S, Perez Velazquez JL, Zhang L, Bechberger JF, Carlen PL, Naus CC (2003) Changes in neuronal migration in neocortex of connexin43 null mutant mice. J Neuropathol Exp Neurol 62(3):304–314, Epub 2003/03/18PubMedGoogle Scholar
  35. Gaietta G, Deerinck TJ, Adams SR, Bouwer J, Tour O, Laird DW et al (2002) Multicolor and electron microscopic imaging of connexin trafficking. Science 296(5567):503–507, Epub 2002/04/20PubMedGoogle Scholar
  36. Garg S, Md Syed M, Kielian T (2005) Staphylococcus aureus-derived peptidoglycan induces Cx43 expression and functional gap junction intercellular communication in microglia. J Neurochem 95(2):475–483, Epub 2005/09/30PubMedGoogle Scholar
  37. Giaume C, Tabernero A, Medina JM (1997) Metabolic trafficking through astrocytic gap junctions. Glia 21(1):114–123, Epub 1997/09/23PubMedGoogle Scholar
  38. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140(6):918–934, Epub 2010/03/23PubMedGoogle Scholar
  39. Goldberg GS, Lampe PD, Nicholson BJ (1999) Selective transfer of endogenous metabolites through gap junctions composed of different connexins. Nat Cell Biol 1(7):457–459, Epub 1999/11/24PubMedGoogle Scholar
  40. Goldberg GS, Moreno AP, Lampe PD (2002) Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP. J Biol Chem 277(39):36725–36730, Epub 2002/07/18PubMedGoogle Scholar
  41. Goldberg GS, Valiunas V, Brink PR (2004) Selective permeability of gap junction channels. Biochim Biophys Acta 1662(1–2):96–101, Epub 2004/03/23PubMedGoogle Scholar
  42. Harris AL (2001) Emerging issues of connexin channels: biophysics fills the gap. Q Rev Biophys 34(3):325–472, Epub 2002/02/13PubMedGoogle Scholar
  43. Harris AL (2007) Connexin channel permeability to cytoplasmic molecules. Prog Biophys Mol Biol 94(1–2):120–143, Epub 2007/05/02PubMedGoogle Scholar
  44. Hartfield EM, Rinaldi F, Glover CP, Wong LF, Caldwell MA, Uney JB (2011) Connexin 36 expression regulates neuronal differentiation from neural progenitor cells. PLoS One 6(3):e14746, Epub 2011/03/17PubMedGoogle Scholar
  45. Hormuzdi SG, Pais I, LeBeau FE, Towers SK, Rozov A, Buhl EH et al (2001) Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron 31(3):487–495, Epub 2001/08/23PubMedGoogle Scholar
  46. Hunter AW, Jourdan J, Gourdie RG (2003) Fusion of GFP to the carboxyl terminus of connexin43 increases gap junction size in HeLa cells. Cell Commun Adhes 10(4–6):211–214, Epub 2003/12/19PubMedGoogle Scholar
  47. Jefferys JG (1995) Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. Physiol Rev 75(4):689–723, Epub 1995/10/01PubMedGoogle Scholar
  48. Kalogeris T, Baines CP, Krenz M, Korthuis RJ (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317, Epub 2012/08/11PubMedGoogle Scholar
  49. Kawasaki A, Hayashi T, Nakachi K, Trosko JE, Sugihara K, Kotake Y et al (2009) Modulation of connexin 43 in rotenone-induced model of Parkinson’s disease. Neuroscience 160(1):61–68, Epub 2009/02/24PubMedGoogle Scholar
  50. Kielian T (2008) Glial connexins and gap junctions in CNS inflammation and disease. J Neurochem 106(3):1000–1016, Epub 2008/04/16PubMedGoogle Scholar
  51. Koulakoff A, Mei X, Orellana JA, Saez JC, Giaume C (2012) Glial connexin expression and function in the context of Alzheimer’s disease. Biochim Biophys Acta 1818(8):2048–2057, Epub 2011/10/20PubMedGoogle Scholar
  52. Laird DW (2006) Life cycle of connexins in health and disease. Biochem J 394(Pt 3):527–543, Epub 2006/02/24PubMedGoogle Scholar
  53. Laird DW (2010) The gap junction proteome and its relationship to disease. Trends Cell Biol 20(2):92–101, Epub 2009/12/01PubMedGoogle Scholar
  54. Leithe E, Rivedal E (2007) Ubiquitination of gap junction proteins. J Membr Biol 217(1–3):43–51, Epub 2007/07/28PubMedGoogle Scholar
  55. Lo CW, Waldo KL, Kirby ML (1999) Gap junction communication and the modulation of cardiac neural crest cells. Trends Cardiovasc Med 9(3–4):63–69, Epub 1999/12/01PubMedGoogle Scholar
  56. Loewenstein WR (1967) On the genesis of cellular communication. Dev Biol 15(6):503–520, Epub 1967/06/01PubMedGoogle Scholar
  57. Lopez P, Balicki D, Buehler LK, Falk MM, Chen SC (2001) Distribution and dynamics of gap junction channels revealed in living cells. Cell Commun Adhes 8(4–6):237–242, Epub 2002/06/18PubMedGoogle Scholar
  58. Lutz SE, Raine CS, Brosnan CF (2012) Loss of astrocyte connexins 43 and 30 does not significantly alter susceptibility or severity of acute experimental autoimmune encephalomyelitis in mice. J Neuroimmunol 245(1–2):8–14, Epub 2012/02/22PubMedGoogle Scholar
  59. Markoullis K, Sargiannidou I, Gardner C, Hadjisavvas A, Reynolds R, Kleopa KA (2012) Disruption of oligodendrocyte gap junctions in experimental autoimmune encephalomyelitis. Glia 60(7):1053–1066, Epub 2012/03/31PubMedGoogle Scholar
  60. 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
  61. Matsushita T, Masaki K, Suzuki S, Matsuoka T, Yonekawa T, Wu XM et al (2011) [Astrocytopathy in neuromyelitis optica, multiple sclerosis and Balo’s disease]. Rinsho Shinkeigaku 51(11):898–900PubMedGoogle Scholar
  62. Menichella DM, Goodenough DA, Sirkowski E, Scherer SS, Paul DL (2003) Connexins are critical for normal myelination in the CNS. J Neurosci 23(13):5963–5973, Epub 2003/07/05PubMedGoogle Scholar
  63. 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
  64. Nadarajah B, Thomaidou D, Evans WH, Parnavelas JG (1996) Gap junctions in the adult cerebral cortex: regional differences in their distribution and cellular expression of connexins. J Comp Neurol 376(2):326–342, Epub 1996/12/09PubMedGoogle Scholar
  65. Nagy JI, Rash JE (2000) Connexins and gap junctions of astrocytes and oligodendrocytes in the CNS. Brain Res Brain Res Rev 32(1):29–44, Epub 2000/04/07PubMedGoogle Scholar
  66. Nagy JI, Ionescu AV, Lynn BD, Rash JE (2003) Coupling of astrocyte connexins Cx26, Cx30, Cx43 to oligodendrocyte Cx29, Cx32, Cx47: implications from normal and connexin32 knockout mice. Glia 44(3):205–218, Epub 2003/11/07PubMedGoogle Scholar
  67. Naus CC, Bechberger JF, Zhang Y, Venance L, Yamasaki H, Juneja SC et al (1997) Altered gap junctional communication, intercellular signaling, and growth in cultured astrocytes deficient in connexin43. J Neurosci Res 49(5):528–540, Epub 1997/09/25PubMedGoogle Scholar
  68. 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
  69. Orellana JA, Saez PJ, Shoji KF, Schalper KA, Palacios-Prado N, Velarde V et al (2009) Modulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration. Antioxid Redox Signal 11(2):369–399, Epub 2008/09/26PubMedGoogle Scholar
  70. Orellana JA, Shoji KF, Abudara V, Ezan P, Amigou E, Saez PJ et al (2011) Amyloid beta-induced death in neurons involves glial and neuronal hemichannels. J Neurosci 31(13):4962–4977, Epub 2011/04/01PubMedGoogle Scholar
  71. Orthmann-Murphy JL, Freidin M, Fischer E, Scherer SS, Abrams CK (2007) Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. J Neurosci 27(51):13949–13957, Epub 2007/12/21PubMedGoogle Scholar
  72. Parenti R, Campisi A, Vanella A, Cicirata F (2002) Immunocytochemical and RT-PCR analysis of connexin36 in cultures of mammalian glial cells. Arch Ital Biol 140(2):101–108, Epub 2002/05/15PubMedGoogle Scholar
  73. Paul DL (1995) New functions for gap junctions. Curr Opin Cell Biol 7(5):665–672, Epub 1995/10/01PubMedGoogle Scholar
  74. Peracchia C (1980) Structural correlates of gap junction permeation. Int Rev Cytol 66:81–146, Epub 1980/01/01PubMedGoogle Scholar
  75. Ransom B, Behar T, Nedergaard M (2003) New roles for astrocytes (stars at last). Trends Neurosci 26(10):520–522, Epub 2003/10/03PubMedGoogle Scholar
  76. Rash JE, Yasumura T, Dudek FE, Nagy JI (2001) Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons. J Neurosci 21(6):1983–2000, Epub 2001/03/14PubMedGoogle Scholar
  77. Rash JE, Olson CO, Davidson KG, Yasumura T, Kamasawa N, Nagy JI (2007) Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus. Neuroscience 147(4):938–956, Epub 2007/07/03PubMedGoogle Scholar
  78. Rawanduzy A, Hansen A, Hansen TW, Nedergaard M (1997) Effective reduction of infarct volume by gap junction blockade in a rodent model of stroke. J Neurosurg 87(6):916–920, Epub 1997/12/31PubMedGoogle Scholar
  79. Retamal MA, Schalper KA, Shoji KF, Bennett MV, Saez JC (2007) Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential. Proc Natl Acad Sci U S A 104(20):8322–8327, Epub 2007/05/15PubMedGoogle Scholar
  80. Revel JP, Yee AG, Hudspeth AJ (1971) Gap junctions between electrotonically coupled cells in tissue culture and in brown fat. Proc Natl Acad Sci U S A 68(12):2924–2927, Epub 1971/12/01PubMedGoogle Scholar
  81. Rouach N, Avignone E, Meme W, Koulakoff A, Venance L, Blomstrand F et al (2002) Gap junctions and connexin expression in the normal and pathological central nervous system. Biol Cell 94(7–8):457–475, Epub 2003/02/05PubMedGoogle Scholar
  82. Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C (2008) Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322(5907):1551–1555, Epub 2008/12/06PubMedGoogle Scholar
  83. Rufer M, Wirth SB, Hofer A, Dermietzel R, Pastor A, Kettenmann H et al (1996) Regulation of connexin-43, GFAP, and FGF-2 is not accompanied by changes in astroglial coupling in MPTP-lesioned, FGF-2-treated parkinsonian mice. J Neurosci Res 46(5):606–617, Epub 1996/12/01PubMedGoogle Scholar
  84. Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC (2003) Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev 83(4):1359–1400, Epub 2003/09/25PubMedGoogle Scholar
  85. Scemes E, Dermietzel R, Spray DC (1998) Calcium waves between astrocytes from Cx43 knockout mice. Glia 24(1):65–73, Epub 1998/08/13PubMedGoogle Scholar
  86. Schwarzmann G, Wiegandt H, Rose B, Zimmerman A, Ben-Haim D, Loewenstein WR (1981) Diameter of the cell-to-cell junctional membrane channels as probed with neutral molecules. Science 213(4507):551–553, Epub 1981/07/31PubMedGoogle Scholar
  87. Sohl G, Maxeiner S, Willecke K (2005) Expression and functions of neuronal gap junctions. Nat Rev Neurosci 6(3):191–200, Epub 2005/03/02PubMedGoogle Scholar
  88. Solan JL, Lampe PD (2009) Connexin43 phosphorylation: structural changes and biological effects. Biochem J 419(2):261–272, Epub 2009/03/25PubMedGoogle Scholar
  89. Sung JY, Lee HJ, Jeong EI, Oh Y, Park J, Kang KS et al (2007) Alpha-synuclein overexpression reduces gap junctional intercellular communication in dopaminergic neuroblastoma cells. Neurosci Lett 416(3):289–293, Epub 2007/03/06PubMedGoogle Scholar
  90. Sutor B, Schmolke C, Teubner B, Schirmer C, Willecke K (2000) Myelination defects and neuronal hyperexcitability in the neocortex of connexin 32-deficient mice. Cereb Cortex 10(7):684–697, Epub 2000/07/25PubMedGoogle Scholar
  91. Tabernero A, Medina JM, Giaume C (2006) Glucose metabolism and proliferation in glia: role of astrocytic gap junctions. J Neurochem 99(4):1049–1061, Epub 2006/08/11PubMedGoogle Scholar
  92. Takeuchi H (2010) Neurotoxicity by microglia: mechanisms and potential therapeutic strategy. Clin Exp Neuroimmunol 1(1):12–21Google Scholar
  93. Takeuchi H, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R et al (2006) Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem 281(30):21362–21368, Epub 2006/05/25PubMedGoogle Scholar
  94. Takeuchi H, Jin S, Suzuki H, Doi Y, Liang J, Kawanokuchi J et al (2008) Blockade of microglial glutamate release protects against ischemic brain injury. Exp Neurol 214(1):144–146, Epub 2008/09/09PubMedGoogle Scholar
  95. Takeuchi H, Mizoguchi H, Doi Y, Jin S, Noda M, Liang J et al (2011) Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer’s disease. PLoS One 6(6):e21108, Epub 2011/06/30PubMedGoogle Scholar
  96. Tamura K, Alessandri B, Heimann A, Kempski O (2011) The effect of a gap-junction blocker, carbenoxolone, on ischemic brain injury and cortical spreading depression. Neuroscience 194:262–271, Epub 2011/08/16PubMedGoogle Scholar
  97. Teubner B, Odermatt B, Guldenagel M, Sohl G, Degen J, Bukauskas F et al (2001) Functional expression of the new gap junction gene connexin47 transcribed in mouse brain and spinal cord neurons. J Neurosci 21(4):1117–1126, Epub 2001/02/13PubMedGoogle Scholar
  98. Teubner B, Michel V, Pesch J, Lautermann J, Cohen-Salmon M, Sohl G et al (2003) Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential. Hum Mol Genet 12(1):13–21, Epub 2002/12/20PubMedGoogle Scholar
  99. Thompson RJ, Zhou N, MacVicar BA (2006) Ischemia opens neuronal gap junction hemichannels. Science 312(5775):924–927PubMedGoogle Scholar
  100. Valiunas V, Polosina YY, Miller H, Potapova IA, Valiuniene L, Doronin S et al (2005) Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions. J Physiol 568(Pt 2):459–468, Epub 2005/07/23PubMedGoogle Scholar
  101. Wallraff A, Odermatt B, Willecke K, Steinhauser C (2004) Distinct types of astroglial cells in the hippocampus differ in gap junction coupling. Glia 48(1):36–43, Epub 2004/08/25PubMedGoogle Scholar
  102. Wallraff A, Kohling R, Heinemann U, Theis M, Willecke K, Steinhauser C (2006) The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J Neurosci 26(20):5438–5447, Epub 2006/05/19PubMedGoogle Scholar
  103. Walz W, Hertz L (1983) Functional interactions between neurons and astrocytes. II. Potassium homeostasis at the cellular level. Prog Neurobiol 20(1–2):133–183, Epub 1983/01/01PubMedGoogle Scholar
  104. Wang J, Ma M, Locovei S, Keane RW, Dahl G (2007) Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters. Am J Physiol Cell Physiol 293(3):C1112–C1119, Epub 2007/07/27PubMedGoogle Scholar
  105. Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, Guldenagel M et al (2002) Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem 383(5):725–737, Epub 2002/07/11PubMedGoogle Scholar
  106. Wong RO, Chernjavsky A, Smith SJ, Shatz CJ (1995) Early functional neural networks in the developing retina. Nature 374(6524):716–718, Epub 1995/04/20PubMedGoogle Scholar
  107. Xu X, Li WE, Huang GY, Meyer R, Chen T, Luo Y et al (2001) Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap junctions. J Cell Biol 154(1):217–230, Epub 2001/07/13PubMedGoogle Scholar
  108. Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Yamashita H, Gutmann DH et al (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11(3):251–253, Epub 2008/02/05PubMedGoogle Scholar
  109. Yawata I, Takeuchi H, Doi Y, Liang J, Mizuno T, Suzumura A (2008) Macrophage-induced neurotoxicity is mediated by glutamate and attenuated by glutaminase inhibitors and gap junction inhibitors. Life Sci 82(21–22):1111–1116, Epub 2008/05/03PubMedGoogle Scholar
  110. Yeager M, Harris AL (2007) Gap junction channel structure in the early 21st century: facts and fantasies. Curr Opin Cell Biol 19(5):521–528, Epub 2007/10/20PubMedGoogle Scholar
  111. Zlomuzica A, Reichinnek S, Maxeiner S, Both M, May E, Worsdorfer P et al (2010) Deletion of connexin45 in mouse neurons disrupts one-trial object recognition and alters kainate-induced gamma-oscillations in the hippocampus. Physiol Behav 101(2):245–253, Epub 2010/05/18PubMedGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Neuroimmunology, Research Institute of Environmental MedicineNagoya UniversityNagoyaJapan

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