Roles of gap junctions, connexins, and pannexins in epilepsy

Frontiers in Physiology

Volumn 5 MAY, Issue , 2014, Pages

  Mylvaganam, Shanthini ^a   Ramani, Meera ^a   Krawczyk, Michal ^a   Carlen, Peter L ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Animal models; Connexins; Epilepsy; Gap junctions; Glia; Human cerebral tissue; Neurons; Pannexins

Indexed keywords

AMMONIUM CHLORIDE; CARBENOXOLONE; FENAMIC ACID DERIVATIVE; FLUFENAMIC ACID; GADOLINIUM; GAP JUNCTION PROTEIN; LANTHANUM; MECLOFENAMIC ACID; MEFLOQUINE; NIFLUMIC ACID; PANNEXIN; PROTEOME; QUININE; TRIMETHYLAMINE; UNCLASSIFIED DRUG;

AMYGDALOID NUCLEUS; BRAIN CORTEX; CX30 GENE; CX32 GENE; CX36 GENE; CX43 GENE; DRUG EFFICACY; EPILEPSY; EPILEPTIC DISCHARGE; GAP JUNCTION; GENE; GENE EXPRESSION; GENE MUTATION; HIPPOCAMPUS; HUMAN; INTRACTABLE EPILEPSY; NEOCORTEX; NONHUMAN; PANX1 GENE; PANX2 GENE; PATHOGENESIS; PROTEIN FUNCTION; REVIEW; TEMPORAL LOBE EPILEPSY; TONIC CLONIC SEIZURE;

EID: 84904350388     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2014.00172     Document Type: Review

References (158)

1. Allen, N. J., Bennett, M. L., Foo, L. C., Wang, G. X., Chakraborty, C., Smith, S. J., et al. (2012). Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature 486, 410-414. doi: 10.1038/nature11059.
2. Andrade-Rozental, A. F., Rozental, R., Hopperstad, M. G., Wu, J. K., Vrionis, F. D., and Spray, D. C. (2000). Gap junctions: the "kiss of death" and the "kiss of life." Brain Res. Brain Res. Rev. 32, 308-315. doi: 10.1016/S0165-0173(99)00099-5.
3. Aronica, E., Gorter, J. A., Jansen, G. H., Leenstra, S., Yankaya, B., and Troost, D. (2001). Expression of connexin 43 and connexin 32 gap-junction proteins in epilepsy-associated brain tumors and in the perilesional epileptic cortex. Acta Neuropathol. 101, 449-459. doi: 10.1007/s004010000305.
4. Badaut, J., Ashwal, S., Adami, A., Tone, B., Recker, R., Spagnoli, D., et al. (2011). Brain water mobility decreases after astrocytic aquaporin-4 inhibition using RNA interference. J. Cereb. Blood Flow Metab. 31, 819-831. doi: 10.1038/jcbfm.2010.163.
5. Bao, L., Locovei, S., and Dahl, G. (2004). Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett. 572, 65-68. doi: 10.1016/j.febslet.2004.07.009.
6. Baranova, A., Ivanov, D., Petrash, N., Pestova, A., Skoblov, M., Kelmanson, I., et al. (2004). The mammalian pannexin family is homologous to the invertebrate innexin gap junction proteins. Genomics 83, 706-716. doi: 10.1016/j.ygeno.2003.09.025.
7. Beenhakker, M. P., and Huguenard, J. R. (2009). Neurons that fire together also conspire together: is normal sleep circuitry hijacked to generate epilepsy? Neuron 62, 612-632. doi: 10.1016/j.neuron.2009.05.015.
8. Beheshti, S., Sayyah, M., Golkar, M., Sepehri, H., Babaie, J., and Vaziri, B. (2010). Changes in hippocampal connexin 36 mRNA and protein levels during epileptogenesis in the kindling model of epilepsy. Prog. Neuropsychopharmacol. Biol. Psychiatry 34, 510-515. doi: 10.1016/j.pnpbp.2010.02.006.
9. Behrens, C. J., Ul Haq, R., Liotta, A., Anderson, M. L., and Heinemann, U. (2011). Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro. Neuroscience 192, 11-19. doi: 10.1016/j.neuroscience.2011.07.015.
10. Behrens, C. J., Van Den Boom, L. P., and Heinemann, U. (2007). Effects of the GABA(A) receptor antagonists bicuculline and gabazine on stimulus-induced sharp wave-ripple complexes in adult rat hippocampus in vitro. Eur. J. Neurosci. 25, 2170-2181. doi: 10.1111/j.1460-9568.2007.05462.x.
11. Belousov, A. B., and Fontes, J. D. (2013). Neuronal gap junction coupling as the primary determinant of the extent of glutamate-mediated excitotoxicity. J. Neural Transm. doi: 10.1007/s00702-013-1109-7. [Epub ahead of print].
12. Bennett, M. V., Contreras, J. E., Bukauskas, F. F., and Saez, J. C. (2003). New roles for astrocytes: gap junction hemichannels have something to communicate. Trends Neurosci. 26, 610-617. doi: 10.1016/j.tins.2003.09.008.
13. Boassa, D., Ambrosi, C., Qiu, F., Dahl, G., Gaietta, G., and Sosinsky, G. (2007). Pannexin1 channels contain a glycosylation site that targets the hexamer to the plasma membrane. J. Biol. Chem. 282, 31733-31743. doi: 10.1074/jbc.M702422200.
14. Boison, D., Sandau, U. S., Ruskin, D. N., Kawamura, M. Jr., and Masino, S. A. (2013). Homeostatic control of brain function-new approaches to understand epileptogenesis. Front. Cell. Neurosci. 7:109. doi: 10.3389/fncel.2013.00109.
15. Bostanci, M. O., and Bagirici, F. (2007). Anticonvulsive effects of carbenoxolone on penicillin-induced epileptiform activity: an in vivo study. Neuropharmacology 52, 362-367. doi: 10.1016/j.neuropharm.2006.08.008.
16. Bostanci, M. O., Bagirici, F., and Canan, S. (2006). A calcium channel blocker flunarizine attenuates the neurotoxic effects of iron. Cell Biol. Toxicol. 22, 119-125. doi: 10.1007/s10565-006-0037-9.
17. Bragin, A., Wilson, C. L., and Engel, J. Jr. (2007). Voltage depth profiles of high-frequency oscillations after kainic acid-induced status epilepticus. Epilepsia 48(Suppl. 5), 35-40. doi: 10.1111/j.1528-1167.2007.01287.x.
18. Bruzzone, R., Barbe, M. T., Jakob, N. J., and Monyer, H. (2005). Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytes. J. Neurochem. 92, 1033-1043. doi: 10.1111/j.1471-4159.2004.02947.x.
19. Buhl, D. L., Harris, K. D., Hormuzdi, S. G., Monyer, H., and Buzsaki, G. (2003). Selective impairment of hippocampal gamma oscillations in connexin-36 knock-out mouse in vivo. J. Neurosci. 23, 1013-1018.
20. Carlen, P. L. (2012). Curious and contradictory roles of glial connexins and pannexins in epilepsy. Brain Res. 1487, 54-60. doi: 10.1016/j.brainres.2012.06.059.
21. Carlen, P. L., Skinner, F., Zhang, L., Naus, C., Kushnir, M., and Perez Velazquez, J. L. (2000). The role of gap junctions in seizures. Brain Res. Brain Res. Rev. 32, 235-241. doi: 10.1016/S0165-0173(99)00084-3.
22. Chang, M., Werner, R., and Dahl, G. (1996). A role for an inhibitory connexin in testis? Dev. Biol. 175, 50-56. doi: 10.1006/dbio.1996.0094.
23. Chen, V. C., Gouw, J. W., Naus, C. C., and Foster, L. J. (2013). Connexin multi-site phosphorylation: mass spectrometry-based proteomics fills the gap. Biochim. Biophys. Acta 1828, 23-34. doi: 10.1016/j.bbamem.2012.02.028.
24. Cherian, P. P., Siller-Jackson, A. J., Gu, S., Wang, X., Bonewald, L. F., Sprague, E., et al. (2005). Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Mol. Biol. Cell 16, 3100-3106. doi: 10.1091/mbc.E04-10-0912.
25. Collignon, F., Wetjen, N. M., Cohen-Gadol, A. A., Cascino, G. D., Parisi, J., Meyer, F. B., et al. (2006). Altered expression of connexin subtypes in mesial temporal lobe epilepsy in humans. J. Neurosurg. 105, 77-87. doi: 10.3171/jns.2006.105.1.77.
26. Condorelli, D. F., Mudo, G., Trovato-Salinaro, A., Mirone, M. B., Amato, G., and Belluardo, N. (2002). Connexin-30 mRNA is up-regulated in astrocytes and expressed in apoptotic neuronal cells of rat brain following kainate-induced seizures. Mol. Cell. Neurosci. 21, 94-113. doi: 10.1006/mcne.2002.1155.
27. Condorelli, D. F., Trovato-Salinaro, A., Mudo, G., Mirone, M. B., and Belluardo, N. (2003). Cellular expression of connexins in the rat brain: neuronal localization, effects of kainate-induced seizures and expression in apoptotic neuronal cells. Eur. J. Neurosci. 18, 1807-1827. doi: 10.1046/j.1460-9568.2003.02910.x.
28. Cruikshank, S. J., Hopperstad, M., Younger, M., Connors, B. W., Spray, D. C., and Srinivas, M. (2004). Potent block of Cx36 and Cx50 gap junction channels by mefloquine. Proc. Natl. Acad. Sci. U.S.A. 101, 12364-12369. doi: 10.1073/pnas.0402044101.
29. Dahl, G. (2007). Gap junction-mimetic peptides do work, but in unexpected ways. Cell Commun. Adhes. 14, 259-264. doi: 10.1080/15419060801891018.
30. Dahl, G., Nonner, W., and Werner, R. (1994). Attempts to define functional domains of gap junction proteins with synthetic peptides. Biophys. J. 67, 1816-1822. doi: 10.1016/S0006-3495(94)80663-0.
31. De Lanerolle, N. C., and Lee, T. S. (2005). New facets of the neuropathology and molecular profile of human temporal lobe epilepsy. Epilepsy Behav. 7, 190-203. doi: 10.1016/j.yebeh.2005.06.003.
32. De Lanerolle, N. C., Lee, T. S., and Spencer, D. D. (2010). Astrocytes and epilepsy. Neurotherapeutics 7, 424-438. doi: 10.1016/j.nurt.2010.08.002.
33. Dietzel, I., and Heinemann, U. (1986). Dynamic variations of the brain cell microenvironment in relation to neuronal hyperactivity. Ann. N.Y. Acad. Sci. 481, 72-86.
34. Dityatev, A., and Rusakov, D. A. (2011). Molecular signals of plasticity at the tetrapartite synapse. Curr. Opin. Neurobiol. 21, 353-359. doi: 10.1016/j.conb.2010.12.006.
35. Dobrowolski, R., Sommershof, A., and Willecke, K. (2007). Some oculodentodigital dysplasia-associated Cx43 mutations cause increased hemichannel activity in addition to deficient gap junction channels. J. Membr. Biol. 219, 9-17. doi: 10.1007/s00232-007-9055-7.
36. Draguhn, A., Traub, R. D., Schmitz, D., and Jefferys, J. G. (1998). Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature 394, 189-192. doi: 10.1038/28184.
37. Dudek, F. E., Yasumura, T., and Rash, J. E. (1998). "Non-synaptic" mechanisms in seizures and epileptogenesis. Cell Biol. Int. 22, 793-805. doi: 10.1006/cbir.1999.0397.
38. Ebihara, L. (2003). Physiology and biophysics of hemi-gap-junctional channels expressed in Xenopus oocytes. Acta Physiol. Scand. 179, 5-8. doi: 10.1046/j.1365-201X.2003.01195.x.
39. Ebihara, L., Liu, X., and Pal, J. D. (2003). Effect of external magnesium and calcium on human connexin46 hemichannels. Biophys. J. 84, 277-286. doi: 10.1016/S0006-3495(03)74848-6.
40. Elisevich, K., Rempel, S. A., Smith, B., and Hirst, K. (1998). Temporal profile of connexin 43 mRNA expression in a tetanus toxin-induced seizure disorder. Mol. Chem. Neuropathol. 35, 23-37.
41. Elisevich, K., Rempel, S. A., Smith, B. J., and Edvardsen, K. (1997). Hippocampal connexin 43 expression in human complex partial seizure disorder. Exp. Neurol. 145, 154-164. doi: 10.1006/exnr.1997.6467.
42. Evans, W. H., and Boitano, S. (2001). Connexin mimetic peptides: specific inhibitors of gap-junctional intercellular communication. Biochem. Soc. Trans. 29, 606-612. doi: 10.1042/BST0290606.
43. Fisher, R. S., Van Emde Boas, W., Blume, W., Elger, C., Genton, P., Lee, P., et al. (2005). Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46, 470-472. doi: 10.1111/j.0013-9580.2005.66104.x.
44. Florence, C. M., Baillie, L. D., and Mulligan, S. J. (2012). Dynamic volume changes in astrocytes are an intrinsic phenomenon mediated by bicarbonate ion flux. PLoS ONE 7:e51124. doi: 10.1371/journal.pone.0051124.
45. Fonseca, C. G., Green, C. R., and Nicholson, L. F. (2002). Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy. Brain Res. 929, 105-116. doi: 10.1016/S0006-8993(01)03289-9.
46. Gajda, Z., Gyengesi, E., Hermesz, E., Ali, K. S., and Szente, M. (2003). Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo. Epilepsia 44, 1596-1600. doi: 10.1111/j.0013-9580.2003.25803.x.
47. Gehi, R., Shao, Q., and Laird, D. W. (2011). Pathways regulating the trafficking and turnover of pannexin1 protein and the role of the C-terminal domain. J. Biol. Chem. 286, 27639-27653. doi: 10.1074/jbc.M111.260711.
48. Giaume, C., Leybaert, L., Naus, C. C., and Saez, J. C. (2013). Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles. Front. Pharmacol. 4:88. doi: 10.3389/fphar.2013.00088.
49. Giaume, C., and Theis, M. (2010). Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system. Brain Res. Rev. 63, 160-176. doi: 10.1016/j.brainresrev.2009.11.005.
50. Gigout, S., Louvel, J., Kawasaki, H., D'antuono, M., Armand, V., Kurcewicz, I., et al. (2006). Effects of gap junction blockers on human neocortical synchronization. Neurobiol. Dis. 22, 496-508. doi: 10.1016/j.nbd.2005.12.011.
51. Hamzei-Sichani, F., Kamasawa, N., Janssen, W. G., Yasumura, T., Davidson, K. G., Hof, P. R., et al. (2007). Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze fracture replica immunogold labeling. Proc. Natl. Acad. Sci. U.S.A. 104, 12548-12553. doi: 10.1073/pnas.0705281104.
52. Harks, E. G., De Roos, A. D., Peters, P. H., De Haan, L. H., Brouwer, A., Ypey, D. L., et al. (2001). Fenamates: a novel class of reversible gap junction blockers. J. Pharmacol. Exp. Ther. 298, 1033-1041.
53. Heinemann, U., Gabriel, S., Jauch, R., Schulze, K., Kivi, A., Eilers, A., et al. (2000). Alterations of glial cell function in temporal lobe epilepsy. Epilepsia 41(Suppl. 6), S185-S189. doi: 10.1111/j.1528-1157.2000.tb01579.x.
54. Hempelmann, A., Heils, A., and Sander, T. (2006). Confirmatory evidence for an association of the connexin-36 gene with juvenile myoclonic epilepsy. Epilepsy Res. 71, 223-228. doi: 10.1016/j.eplepsyres.2006.06.021.
55. Herve, J. C., Derangeon, M., Bahbouhi, B., Mesnil, M., and Sarrouilhe, D. (2007). The connexin turnover, an important modulating factor of the level of cell-to-cell junctional communication: comparison with other integral membrane proteins. J. Membr. Biol. 217, 21-33. doi: 10.1007/s00232-007-9054-8.
56. Herve, J. C., and Dhein, S. (2010). Peptides targeting gap junctional structures. Curr. Pharm. Des. 16, 3056-3070. doi: 10.2174/138161210793292528.
57. Hinterkeuser, S., Schroder, W., Hager, G., Seifert, G., Blumcke, I., Elger, C. E., et al. (2000). Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances. Eur. J. Neurosci. 12, 2087-2096. doi: 10.1046/j.1460-9568.2000.00104.x.
58. Hormuzdi, S. G., Pais, I., Lebeau, F. E., Towers, S. K., Rozov, A., Buhl, E. H., et al. (2001). Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron 31, 487-495. doi: 10.1016/S0896-6273(01)00387-7.
59. Iglesias, R., Locovei, S., Roque, A., Alberto, A. P., Dahl, G., Spray, D. C., et al. (2008). P2X7 receptor-Pannexin1 complex: pharmacology and signaling. Am. J. Physiol. Cell Physiol. 295, C752-C760. doi: 10.1152/ajpcell.00228.2008.
60. Iglesias, R., Spray, D. C., and Scemes, E. (2009). Mefloquine blockade of Pannexin1 currents: resolution of a conflict. Cell Commun. Adhes. 16, 131-137. doi: 10.3109/15419061003642618.
61. Jahromi, S. S., Wentlandt, K., Piran, S., and Carlen, P. L. (2002). Anticonvulsant actions of gap junctional blockers in an in vitro seizure model. J. Neurophysiol. 88, 1893-1902.
62. Jefferys, J. G. (1995). Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. Physiol. Rev. 75, 689-723.
63. Jiang, T., Long, H., Ma, Y., Long, L., Li, Y., Li, F., et al. (2013). Altered expression of pannexin proteins in patients with temporal lobe epilepsy. Mol. Med. Rep. 8, 1801-1806. doi: 10.3892/mmr.2013.1739.
64. Jin, M. M., and Chen, Z. (2011). Role of gap junctions in epilepsy. Neurosci. Bull. 27, 389-406. doi: 10.1007/s12264-011-1944-1.
65. Kardami, E., Dang, X., Iacobas, D. A., Nickel, B. E., Jeyaraman, M., Srisakuldee, W., et al. (2007). The role of connexins in controlling cell growth and gene expression. Prog. Biophys. Mol. Biol. 94, 245-264. doi: 10.1016/j.pbiomolbio.2007.03.009.
66. Khosravani, H., Pinnegar, C. R., Mitchell, J. R., Bardakjian, B. L., Federico, P., and Carlen, P. L. (2005). Increased high-frequency oscillations precede in vitro low-Mg seizures. Epilepsia 46, 1188-1197. doi: 10.1111/j.1528-1167.2005.65604.x.
67. Khurgel, M., and Ivy, G. O. (1996). Astrocytes in kindling: relevance to epileptogenesis. Epilepsy Res. 26, 163-175.
68. Kim, J. E., and Kang, T. C. (2011). The P2X7 receptor-pannexin-1 complex decreases muscarinic acetylcholine receptor-mediated seizure susceptibility in mice. J. Clin. Invest. 121, 2037-2047. doi: 10.1172/JCI44818.
69. +]o in human epileptic non-sclerotic and sclerotic hippocampal area CA1. Eur. J. Neurosci. 12, 2039-2048. doi: 10.1046/j.1460-9568.2000.00103.x.
70. Kohling, R., Gladwell, S. J., Bracci, E., Vreugdenhil, M., and Jefferys, J. G. (2001). Prolonged epileptiform bursting induced by 0-Mg(2+) in rat hippocampal slices depends on gap junctional coupling. Neuroscience 105, 579-587. doi: 10.1016/S0306-4522(01)00222-6.
71. Laird, D. W. (2010). The gap junction proteome and its relationship to disease. Trends Cell Biol. 20, 92-101. doi: 10.1016/j.tcb.2009.11.001.
72. Li, J., Shen, H., Naus, C. C., Zhang, L., and Carlen, P. L. (2001). Upregulation of gap junction connexin 32 with epileptiform activity in the isolated mouse hippocampus. Neuroscience 105, 589-598. doi: 10.1016/S0306-4522(01)00204-4.
73. Lin, J. H., Weigel, H., Cotrina, M. L., Liu, S., Bueno, E., Hansen, A. J., et al. (1998). Gap-junction-mediated propagation and amplification of cell injury. Nat. Neurosci. 1, 494-500. doi: 10.1038/2210.
74. Lin, S. T., Wang, Y., Xue, Y., Feng, D. C., Xu, Y., and Xu, L. Y. (2008). Tetrandrine suppresses LPS-induced astrocyte activation via modulating IKKs-IkappaBalpha-NF-kappaB signaling pathway. Mol. Cell. Biochem. 315, 41-49. doi: 10.1007/s11010-008-9787-4.
75. Liotta, A., Caliskan, G., Ul Haq, R., Hollnagel, J. O., Rosler, A., Heinemann, U., et al. (2011). Partial disinhibition is required for transition of stimulus-induced sharp wave-ripple complexes into recurrent epileptiform discharges in rat hippocampal slices. J. Neurophysiol. 105, 172-187. doi: 10.1152/jn.00186.2010.
76. Liu, H. T., Toychiev, A. H., Takahashi, N., Sabirov, R. Z., and Okada, Y. (2008). Maxi-anion channel as a candidate pathway for osmosensitive ATP release from mouse astrocytes in primary culture. Cell Res. 18, 558-565. doi: 10.1038/cr.2008.49.
77. Loddenkemper, T., Grote, K., Evers, S., Oelerich, M., and Stogbauer, F. (2002). Neurological manifestations of the oculodentodigital dysplasia syndrome. J. Neurol. 249, 584-595. doi: 10.1007/s004150200068.
78. Lohman, A. W., and Isakson, B. E. (2014). Differentiating connexin hemichannels and pannexin channels in cellular ATP release. FEBS Lett. 588, 1379-1388. doi: 10.1016/j.febslet.2014.02.004.
79. Lutz, S. E., Zhao, Y., Gulinello, M., Lee, S. C., Raine, C. S., and Brosnan, C. F. (2009). Deletion of astrocyte connexins 43 and 30 leads to a dysmyelinating phenotype and hippocampal CA1 vacuolation. J. Neurosci. 29, 7743-7752. doi: 10.1523/JNEUROSCI.0341-09.2009.
80. Lux, H. D., and Heinemann, U. (1978). Ionic changes during experimentally induced seizure activity. Electroencephalogr. Clin. Neurophysiol. Suppl. 34, 289-297.
81. Macvicar, B. A., and Thompson, R. J. (2010). Non-junction functions of pannexin-1 channels. Trends Neurosci. 33, 93-102. doi: 10.1016/j.tins.2009.11.007.
82. Magnotti, L. M., Goodenough, D. A., and Paul, D. L. (2011). Deletion of oligodendrocyte Cx32 and astrocyte Cx43 causes white matter vacuolation, astrocyte loss and early mortality. Glia 59, 1064-1074. doi: 10.1002/glia.21179.
83. Maier, N., Nimmrich, V., and Draguhn, A. (2003). Cellular and network mechanisms underlying spontaneous sharp wave-ripple complexes in mouse hippocampal slices. J. Physiol. 550, 873-887. doi: 10.1113/jphysiol.2003.044602.
84. Mas, C., Taske, N., Deutsch, S., Guipponi, M., Thomas, P., Covanis, A., et al. (2004). Association of the connexin36 gene with juvenile myoclonic epilepsy. J. Med. Genet. 41, e93. doi: 10.1136/jmg.2003.017954.
85. Medina-Ceja, L., Cordero-Romero, A., and Morales-Villagran, A. (2008). Antiepileptic effect of carbenoxolone on seizures induced by 4-aminopyridine: a study in the rat hippocampus and entorhinal cortex. Brain Res. 1187, 74-81. doi: 10.1016/j.brainres.2007.10.040.
86. Mlinar, B., and Enyeart, J. J. (1993). Block of current through T-type calcium channels by trivalent metal cations and nickel in neural rat and human cells. J. Physiol. 469, 639-652.
87. Montana, V., Malarkey, E. B., Verderio, C., Matteoli, M., and Parpura, V. (2006). Vesicular transmitter release from astrocytes. Glia 54, 700-715. doi: 10.1002/glia.20367.
88. Montoro, R. J., and Yuste, R. (2004). Gap junctions in developing neocortex: a review. Brain Res. Brain Res. Rev. 47, 216-226. doi: 10.1016/j.brainresrev.2004.06.009.
89. Mylvaganam, S., Zhang, L., Wu, C., Zhang, Z. J., Samoilova, M., Eubanks, J., et al. (2010). Hippocampal seizures alter the expression of the pannexin and connexin transcriptome. J. Neurochem. 112, 92-102. doi: 10.1111/j.1471-4159.2009.06431.x.
90. Nagy, J. I. (2012). Evidence for connexin36 localization at hippocampal mossy fiber terminals suggesting mixed chemical/electrical transmission by granule cells. Brain Res. 1487, 107-122. doi: 10.1016/j.brainres.2012.05.064.
91. Nakahiro, M., Arakawa, O., and Narahashi, T. (1991). Modulation of gamma-aminobutyric acid receptor-channel complex by alcohols. J. Pharmacol. Exp. Ther. 259, 235-240.
92. Naus, C. C., Bechberger, J. F., and Paul, D. L. (1991). Gap junction gene expression in human seizure disorder. Exp. Neurol. 111, 198-203.
93. Nemani, V. M., and Binder, D. K. (2005). Emerging role of gap junctions in epilepsy. Histol. Histopathol. 20, 253-259.
94. Nilsen, K. E., Kelso, A. R., and Cock, H. R. (2006). Antiepileptic effect of gap-junction blockers in a rat model of refractory focal cortical epilepsy. Epilepsia 47, 1169-1175. doi: 10.1111/j.1528-1167.2006.00540.x.
95. Orellana, J. A., Diaz, E., Schalper, K. A., Vargas, A. A., Bennett, M. V., and Saez, J. C. (2011). Cation permeation through connexin 43 hemichannels is cooperative, competitive and saturable with parameters depending on the permeant species. Biochem. Biophys. Res. Commun. 409, 603-609. doi: 10.1016/j.bbrc.2011.05.031.
96. Pais, I., Hormuzdi, S. G., Monyer, H., Traub, R. D., Wood, I. C., Buhl, E. H., et al. (2003). Sharp wave-like activity in the hippocampus in vitro in mice lacking the gap junction protein connexin 36. J. Neurophysiol. 89, 2046-2054. doi: 10.1152/jn.0549.2002.
97. Pankratov, Y., Lalo, U., Krishtal, O. A., and Verkhratsky, A. (2009). P2X receptors and synaptic plasticity. Neuroscience 158, 137-148. doi: 10.1016/j.neuroscience.2008.03.076.
98. Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J. Y., et al. (2005). Astrocytic purinergic signaling coordinates synaptic networks. Science 310, 113-116. doi: 10.1126/science.1116916.
99. Patel, D., Zhang, X., and Veenstra, R. D. (2014). Connexin hemichannel and pannexin channel electrophysiology: How do they differ? FEBS Lett. 588, 1372-1378. doi: 10.1016/j.febslet.2013.12.023.
100. Penuela, S., Bhalla, R., Gong, X. Q., Cowan, K. N., Celetti, S. J., Cowan, B. J., et al. (2007). Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J. Cell Sci. 120, 3772-3783. doi: 10.1242/jcs.009514.
101. Penuela, S., Bhalla, R., Nag, K., and Laird, D. W. (2009). Glycosylation regulates pannexin intermixing and cellular localization. Mol. Biol. Cell 20, 4313-4323. doi: 10.1091/mbc.E09-01-0067.
102. Pereda, A. E. (2014). Electrical synapses and their functional interactions with chemical synapses. Nat. Rev. Neurosci. 15, 250-263. doi: 10.1038/nrn3708.
103. Perez Velazquez, J. L., and Carlen, P. L. (2000). Gap junctions, synchrony and seizures. Trends Neurosci. 23, 68-74. doi: 10.1016/S0166-2236(99)01497-6.
104. Perez-Velazquez, J. L., Valiante, T. A., and Carlen, P. L. (1994). Modulation of gap junctional mechanisms during calcium-free induced field burst activity: a possible role for electrotonic coupling in epileptogenesis. J. Neurosci. 14, 4308-4317.
105. Rakhade, S. N., and Jensen, F. E. (2009). Epileptogenesis in the immature brain: emerging mechanisms. Nat. Rev. Neurol. 5, 380-391. doi: 10.1038/nrneurol.2009.80.
106. Retamal, M. A., Schalper, K. A., Shoji, K. F., Bennett, M. V., and Saez, J. C. (2007). Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential. Proc. Natl. Acad. Sci. U.S.A. 104, 8322-8327. doi: 10.1073/pnas.0702456104.
107. Risher, W. C., and Eroglu, C. (2012). Thrombospondins as key regulators of synaptogenesis in the central nervous system. Matrix Biol. 31, 170-177. doi: 10.1016/j.matbio.2012.01.004.
108. Ross, F. M., Gwyn, P., Spanswick, D., and Davies, S. N. (2000). Carbenoxolone depresses spontaneous epileptiform activity in the CA1 region of rat hippocampal slices. Neuroscience 100, 789-796. doi: 10.1016/S0306-4522(00)00346-8.
109. Rouach, N., Koulakoff, A., Abudara, V., Willecke, K., and Giaume, C. (2008). Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322, 1551-1555. doi: 10.1126/science.1164022.
110. Rouach, N., Segal, M., Koulakoff, A., Giaume, C., and Avignone, E. (2003). Carbenoxolone blockade of neuronal network activity in culture is not mediated by an action on gap junctions. J. Physiol. 553, 729-745. doi: 10.1113/jphysiol.2003.053439.
111. Rozental, R., Andrade-Rozental, A. F., Zheng, X., Urban, M., Spray, D. C., and Chiu, F. C. (2001). Gap junction-mediated bidirectional signaling between human fetal hippocampal neurons and astrocytes. Dev. Neurosci. 23, 420-431. doi: 10.1159/000048729.
112. Rozental, R., Srinivas, M., Gokhan, S., Urban, M., Dermietzel, R., Kessler, J. A., et al. (2000). Temporal expression of neuronal connexins during hippocampal ontogeny. Brain Res. Brain Res. Rev. 32, 57-71. doi: 10.1016/S0165-0173(99)00096-X.
113. Saez, J. C., Retamal, M. A., Basilio, D., Bukauskas, F. F., and Bennett, M. V. (2005). Connexin-based gap junction hemichannels: gating mechanisms. Biochim. Biophys. Acta 1711, 215-224. doi: 10.1016/j.bbamem.2005.01.014.
114. Salameh, A., and Dhein, S. (2005). Pharmacology of gap junctions. New pharmacological targets for treatment of arrhythmia, seizure and cancer? Biochim. Biophys. Acta 1719, 36-58. doi: 10.1016/j.bbamem.2005.09.007.
115. Samoilova, M., Li, J., Pelletier, M. R., Wentlandt, K., Adamchik, Y., Naus, C. C., et al. (2003). Epileptiform activity in hippocampal slice cultures exposed chronically to bicuculline: increased gap junctional function and expression. J. Neurochem. 86, 687-699. doi: 10.1046/j.1471-4159.2003.01893.x.
116. Samoilova, M., Wentlandt, K., Adamchik, Y., Velumian, A. A., and Carlen, P. L. (2008). Connexin 43 mimetic peptides inhibit spontaneous epileptiform activity in organotypic hippocampal slice cultures. Exp. Neurol. 210, 762-775. doi: 10.1016/j.expneurol.2008.01.005.
117. Santiago, M. F., Veliskova, J., Patel, N. K., Lutz, S. E., Caille, D., Charollais, A., et al. (2011). Targeting pannexin1 improves seizure outcome. PLoS ONE 6:e25178. doi: 10.1371/journal.pone.0025178.
118. Sayyah, M., Kaviani, B., Khoshkholgh-Sima, B., Bagheri, M., Olad, M., Choopani, S., et al. (2012). Effect of chronic intracerebroventricluar administration of lipopolysaccharide on connexin43 protein expression in rat hippocampus. Iran. Biomed. J. 16, 25-32. doi: 10.6091/IBJ.1030.2012.
119. Scemes, E., Spray, D. C., and Meda, P. (2009). Connexins, pannexins, innexins: novel roles of "hemi-channels." Pflugers Arch. 457, 1207-1226. doi: 10.1007/s00424-008-0591-5.
120. 2+]i responses. Mol. Biol. Cell 19, 3501-3513. doi: 10.1091/mbc.E07-12-1240.
121. Seifert, G., Schilling, K., and Steinhauser, C. (2006). Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat. Rev. Neurosci. 7, 194-206. doi: 10.1038/nrn1870.
122. Shahar, E., Derchansky, M., and Carlen, P. L. (2009). The role of altered tissue osmolality on the characteristics and propagation of seizure activity in the intact isolated mouse hippocampus. Clin. Neurophysiol. 120, 673-678. doi: 10.1016/j.clinph.2009.01.014.
123. Simeone, T. A., Simeone, K. A., Samson, K. K., Kim Do, Y., and Rho, J. M. (2013). Loss of the Kv1.1 potassium channel promotes pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices. Neurobiol. Dis. 54, 68-81. doi: 10.1016/j.nbd.2013.02.009.
124. Simon, A., Traub, R. D., Vladimirov, N., Jenkins, A., Nicholson, C., Whittaker, R. G., et al. (2013). Gap junction networks can generate both ripple-like and fast ripple-like oscillations. Eur. J. Neurosci. 39, 46-60. doi: 10.1111/ejn.12386.
125. Simon, A., Traub, R. D., Vladimirov, N., Jenkins, A., Nicholson, C., Whittaker, R. G., et al. (2014). Gap junction networks can generate both ripple-like and fast ripple-like oscillations. Eur. J. Neurosci. 39, 46-60. doi: 10.1111/ejn.12386.
126. Sohl, G., Guldenagel, M., Beck, H., Teubner, B., Traub, O., Gutierrez, R., et al. (2000). Expression of connexin genes in hippocampus of kainate-treated and kindled rats under conditions of experimental epilepsy. Brain Res. Mol. Brain Res. 83, 44-51. doi: 10.1016/S0169-328X(00)00195-9.
127. Sohl, G., and Willecke, K. (2004). Gap junctions and the connexin protein family. Cardiovasc. Res. 62, 228-232. doi: 10.1016/j.cardiores.2003.11.013.
128. Somjen, G. G. (2002). Ion regulation in the brain: implications for pathophysiology. Neuroscientist 8, 254-267. doi: 10.1177/1073858402008003011.
129. Srinivas, M., Hopperstad, M. G., and Spray, D. C. (2001). Quinine blocks specific gap junction channel subtypes. Proc. Natl. Acad. Sci. U.S.A. 98, 10942-10947. doi: 10.1073/pnas.191206198.
130. Srinivas, M., and Spray, D. C. (2003). Closure of gap junction channels by arylaminobenzoates. Mol. Pharmacol. 63, 1389-1397. doi: 10.1124/mol.63.6.1389.
131. Staba, R. J., Wilson, C. L., Bragin, A., Jhung, D., Fried, I., and Engel, J. Jr. (2004). High-frequency oscillations recorded in human medial temporal lobe during sleep. Ann. Neurol. 56, 108-115. doi: 10.1002/ana.20164.
132. Steinhauser, C., and Seifert, G. (2002). Glial membrane channels and receptors in epilepsy: impact for generation and spread of seizure activity. Eur. J. Pharmacol. 447, 227-237. doi: 10.1016/S0014-2999(02)01846-0.
133. + channels and gap junction coupling. Glia 60, 1192-1202. doi: 10.1002/glia.22313.
134. Stridh, M. H., Tranberg, M., Weber, S. G., Blomstrand, F., and Sandberg, M. (2008). Stimulated efflux of amino acids and glutathione from cultured hippocampal slices by omission of extracellular calcium: likely involvement of connexin hemichannels. J. Biol. Chem. 283, 10347-10356. doi: 10.1074/jbc.M704153200.
135. Su, M., and Tong, X. X. (2010). [Astrocytic gap junction in the hippocampus of rats with lithium pilocarpine-induced epilepsy]. Nan Fang Yi Ke Da Xue Xue Bao 30, 2738-2741.
136. Sutor, B., and Hagerty, T. (2005). Involvement of gap junctions in the development of the neocortex. Biochim. Biophys. Acta 1719, 59-68. doi: 10.1016/j.bbamem.2005.09.005.
137. Sykova, E. (2004). Diffusion properties of the brain in health and disease. Neurochem. Int. 45, 453-466. doi: 10.1016/j.neuint.2003.11.009.
138. Szente, M., Gajda, Z., Said Ali, K., and Hermesz, E. (2002). Involvement of electrical coupling in the in vivo ictal epileptiform activity induced by 4-aminopyridine in the neocortex. Neuroscience 115, 1067-1078. doi: 10.1016/S0306-4522(02)00533-X.
139. Takahashi, D. K., Vargas, J. R., and Wilcox, K. S. (2010). Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus. Neurobiol. Dis. 40, 573-585. doi: 10.1016/j.nbd.2010.07.018.
140. Thompson, R. J., Jackson, M. F., Olah, M. E., Rungta, R. L., Hines, D. J., Beazely, M. A., et al. (2008). Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus. Science 322, 1555-1559. doi: 10.1126/science.1165209.
141. Thompson, R. J., and Macvicar, B. A. (2008). Connexin and pannexin hemichannels of neurons and astrocytes. Channels 2, 81-86. doi: 10.4161/chan.2.2.6003.
142. Traub, R. D., Contreras, D., and Whittington, M. A. (2005). Combined experimental/simulation studies of cellular and network mechanisms of epileptogenesis in vitro and in vivo. J. Clin. Neurophysiol. 22, 330-342.
143. Traub, R. D., Draguhn, A., Whittington, M. A., Baldeweg, T., Bibbig, A., Buhl, E. H., et al. (2002). Axonal gap junctions between principal neurons: a novel source of network oscillations, and perhaps epileptogenesis. Rev. Neurosci. 13, 1-30. doi: 10.1515/REVNEURO.2002.13.1.1.
144. Traub, R. D., Michelson-Law, H., Bibbig, A. E., Buhl, E. H., and Whittington, M. A. (2004). Gap junctions, fast oscillations and the initiation of seizures. Adv. Exp. Med. Biol. 548, 110-122. doi: 10.1007/978-1-4757-6376-8_9.
145. Traub, R. D., Schmitz, D., Jefferys, J. G., and Draguhn, A. (1999). High-frequency population oscillations are predicted to occur in hippocampal pyramidal neuronal networks interconnected by axoaxonal gap junctions. Neuroscience 92, 407-426.
146. Vazquez, Y., Mendez, B., Trueta, C., and De-Miguel, F. F. (2009). Summation of excitatory postsynaptic potentials in electrically-coupled neurones. Neuroscience 163, 202-212. doi: 10.1016/j.neuroscience.2009.06.003.
147. Verselis, V. K., and Srinivas, M. (2008). Divalent cations regulate connexin hemichannels by modulating intrinsic voltage-dependent gating. J. Gen. Physiol. 132, 315-327. doi: 10.1085/jgp.200810029.
148. Vivar, C., Traub, R. D., and Gutierrez, R. (2012). Mixed electrical-chemical transmission between hippocampal mossy fibers and pyramidal cells. Eur. J. Neurosci. 35, 76-82. doi: 10.1111/j.1460-9568.2011.07930.x.
149. Voss, L. J., Jacobson, G., Sleigh, J. W., Steyn-Ross, A., and Steyn-Ross, M. (2009). Excitatory effects of gap junction blockers on cerebral cortex seizure-like activity in rats and mice. Epilepsia 50, 1971-1978. doi: 10.1111/j.1528-1167.2009.02087.x.
150. Wallraff, A., Kohling, R., Heinemann, U., Theis, M., Willecke, K., and Steinhauser, C. (2006). The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J. Neurosci. 26, 5438-5447. doi: 10.1523/JNEUROSCI.0037-06.2006.
151. Wang, J., Yang, J., Liu, P., Bi, X., Li, C., and Zhu, K. (2012). NAD induces astrocyte calcium flux and cell death by ART2 and P2X7 pathway. Am. J. Pathol. 181, 746-752. doi: 10.1016/j.ajpath.2012.05.019.
152. 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, 725-737. doi: 10.1515/BC.2002.076.
153. Xu, L., Zeng, L. H., and Wong, M. (2009). Impaired astrocytic gap junction coupling and potassium buffering in a mouse model of tuberous sclerosis complex. Neurobiol. Dis. 34, 291-299. doi: 10.1016/j.nbd.2009.01.010.
154. Ylinen, A., Bragin, A., Nadasdy, Z., Jando, G., Szabo, I., Sik, A., et al. (1995). Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms. J. Neurosci. 15, 30-46.
155. Yoon, J. J., Green, C. R., O'carroll, S. J., and Nicholson, L. F. (2010). Dose-dependent protective effect of connexin43 mimetic peptide against neurodegeneration in an ex vivo model of epileptiform lesion. Epilepsy Res. 92, 153-162. doi: 10.1016/j.eplepsyres.2010.08.014.
156. Zador, Z., Weiczner, R., and Mihaly, A. (2008). Long-lasting dephosphorylation of connexin 43 in acute seizures is regulated by NMDA receptors in the rat cerebral cortex. Mol. Med. Rep. 1, 721-727. doi: 10.3892/mmr_00000019.
157. Zhang, X. L., Zhang, L., and Carlen, P. L. (2004). Electrotonic coupling between stratum oriens interneurones in the intact in vitro mouse juvenile hippocampus. J. Physiol. 558, 825-839. doi: 10.1113/jphysiol.2004.065649.
158. Zhang, Z., Chen, G., Zhou, W., Song, A., Xu, T., Luo, Q., et al. (2007). Regulated ATP release from astrocytes through lysosome exocytosis. Nat. Cell Biol. 9, 945-953. doi: 10.1038/ncb1620.