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Are Alterations in Transmitter Receptor and Ion Channel Expression Responsible for Epilepsies?

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Issues in Clinical Epileptology: A View from the Bench

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 813))

Abstract

Neuronal voltage-gated ion channels and ligand-gated synaptic receptors play a critical role in maintaining the delicate balance between neuronal excitation and inhibition within neuronal networks in the brain. Changes in expression of voltage-gated ion channels, in particular sodium, hyperpolarization-activated cyclic nucleotide-gated (HCN) and calcium channels, and ligand-gated synaptic receptors, in particular GABA and glutamate receptors, have been reported in many types of both genetic and acquired epilepsies, in animal models and in humans. In this chapter we review these and discuss the potential pathogenic role they may play in the epilepsies.

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References

  1. Aronica E, Boer K, Doorn KJ, Zurolo E, Spliet WG, van Rijen PC, Baayen JC, Gorter JA, Jeromin A (2009) Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions. Neurobiol Dis 36(1):81–95

    CAS  PubMed  Google Scholar 

  2. Aronica E, van Vliet EA, Mayboroda OA, Troost D, da Silva FH, Gorter JA (2000) Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy. Eur J Neurosci 12(7):2333–2344

    CAS  PubMed  Google Scholar 

  3. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Moshe SL, Nordli D, Plouin P, Scheffer IE (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 51(4):676–685

    PubMed  Google Scholar 

  4. Bernard C, Anderson A, Becker A, Poolos NP, Beck H, Johnston D (2004) Acquired dendritic channelopathy in temporal lobe epilepsy. Science 305(5683):532–535

    CAS  PubMed  Google Scholar 

  5. Blumenfeld H, Klein JP, Schridde U, Vestal M, Rice T, Khera DS, Bashyal C, Giblin K, Paul-Laughinghouse C, Wang F, Phadke A, Mission J, Agarwal RK, Englot DJ, Motelow J, Nersesyan H, Waxman SG, Levin AR (2008) Early treatment suppresses the development of spike-wave epilepsy in a rat model. Epilepsia 49(3):400–409

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Bouilleret V, Loup F, Kiener T, Marescaux C, Fritschy JM (2000) Early loss of interneurons and delayed subunit-specific changes in GABA(A)-receptor expression in a mouse model of mesial temporal lobe epilepsy. Hippocampus 10(3):305–324

    CAS  PubMed  Google Scholar 

  7. Brewster AL, Chen Y, Bender RA, Yeh A, Shigemoto R, Baram TZ (2006) Quantitative analysis and subcellular distribution of mRNA and protein expression of the hyperpolarization-activated cyclic nucleotide-gated channels throughout development in rat hippocampus. Cereb Cortex 17:702–712

    PubMed Central  PubMed  Google Scholar 

  8. Broicher T, Kanyshkova T, Meuth P, Pape HC, Budde T (2008) Correlation of T-channel coding gene expression, IT, and the low threshold Ca2+ spike in the thalamus of a rat model of absence epilepsy. Mol Cell Neurosci 39(3):384–399

    CAS  PubMed  Google Scholar 

  9. Budde T, Caputi L, Kanyshkova T, Staak R, Abrahamczik C, Munsch T, Pape HC (2005) Impaired regulation of thalamic pacemaker channels through an imbalance of subunit expression in absence epilepsy. J Neurosci 25(43):9871–9882

    CAS  PubMed  Google Scholar 

  10. Casillas-Espinosa PM, Powell KL, O’Brien TJ (2012) Regulators of synaptic transmission: roles in the pathogenesis and treatment of epilepsy. Epilepsia 53(Suppl 9):41–58

    CAS  PubMed  Google Scholar 

  11. Chen Y, Lu J, Pan H, Zhang Y, Wu H, Xu K, Liu X, Jiang Y, Bao X, Yao Z, Ding K, Lo WH, Qiang B, Chan P, Shen Y, Wu X (2003) Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol 54(2):239–243

    CAS  PubMed  Google Scholar 

  12. Coenen AM, Van Luijtelaar EL (2003) Genetic animal models for absence epilepsy: a review of the WAG/Rij strain of rats. Behav Genet 33(6):635–655

    CAS  PubMed  Google Scholar 

  13. Conn PJ, Pin JP (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205–237

    CAS  PubMed  Google Scholar 

  14. Cooper EC (2012) Potassium channels (including KCNQ) and epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds) Jasper’s basic mechanisms of the epilepsies, 4th edn. Bethesda, pp 55–65

    Google Scholar 

  15. Danober L, Deransart C, Depaulis A, Vergnes M, Marescaux C (1998) Pathophysiological mechanisms of genetic absence epilepsy in the rat. Prog Neurobiol 55(1):27–57

    CAS  PubMed  Google Scholar 

  16. Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51(1):7–61

    CAS  PubMed  Google Scholar 

  17. Eid T, Kovacs I, Spencer DD, de Lanerolle NC (2002) Novel expression of AMPA-receptor subunit GluR1 on mossy cells and CA3 pyramidal neurons in the human epileptogenic hippocampus. Eur J Neurosci 15(3):517–527

    PubMed  Google Scholar 

  18. Escayg A, Goldin AL (2010) Sodium channel SCN1A and epilepsy: mutations and mechanisms. Epilepsia 51(9):1650–1658

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Frasca A, Aalbers M, Frigerio F, Fiordaliso F, Salio M, Gobbi M, Cagnotto A, Gardoni F, Battaglia GS, Hoogland G, Di Luca M, Vezzani A (2011) Misplaced NMDA receptors in epileptogenesis contribute to excitotoxicity. Neurobiol Dis 43(2):507–515

    CAS  PubMed  Google Scholar 

  20. Fritschy JM, Kiener T, Bouilleret V, Loup F (1999) GABAergic neurons and GABA(A)-receptors in temporal lobe epilepsy. Neurochem Int 34(5):435–445

    CAS  PubMed  Google Scholar 

  21. Furtinger S, Pirker S, Czech T, Baumgartner C, Sperk G (2003) Increased expression of gamma-aminobutyric acid type B receptors in the hippocampus of patients with temporal lobe epilepsy. Neurosci Lett 352(2):141–145

    CAS  PubMed  Google Scholar 

  22. Ghasemi M, Schachter SC (2011) The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav 22(4):617–640

    PubMed  Google Scholar 

  23. Gibson CJ, Meyer RC, Hamm RJ (2010) Traumatic brain injury and the effects of diazepam, diltiazem, and MK-801 on GABA-A receptor subunit expression in rat hippocampus. J Biomed Sci 17:38

    PubMed Central  PubMed  Google Scholar 

  24. Giza CC, Maria NS, Hovda DA (2006) N-methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. J Neurotrauma 23(6):950–961

    PubMed Central  PubMed  Google Scholar 

  25. Gonzalez MI, Brooks-Kayal A (2011) Altered GABA(A) receptor expression during epileptogenesis. Neurosci Lett 497(3):218–222

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Gorter JA, van Vliet EA, Aronica E, Breit T, Rauwerda H, Lopes da Silva FH, Wadman WJ (2006) Potential new antiepileptogenic targets indicated by microarray analysis in a rat model for temporal lobe epilepsy. J Neurosci 26(43):11083–11110

    CAS  PubMed  Google Scholar 

  27. Gorter JA, van Vliet EA, Lopes da Silva FH, Isom LL, Aronica E (2002) Sodium channel beta1-subunit expression is increased in reactive astrocytes in a rat model for mesial temporal lobe epilepsy. Eur J Neurosci 16(2):360–364

    PubMed  Google Scholar 

  28. Hargus NJ, Merrick EC, Nigam A, Kalmar CL, Baheti AR, Bertram EH 3rd, Patel MK (2011) Temporal lobe epilepsy induces intrinsic alterations in Na channel gating in layer II medial entorhinal cortex neurons. Neurobiol Dis 41(2):361–376

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Hauser WA, Annegers JF, Kurland LT (1991) Prevalence of epilepsy in Rochester, Minnesota: 1940–1980. Epilepsia 32(4):429–445

    CAS  PubMed  Google Scholar 

  30. Helbig I, Scheffer IE, Mulley JC, Berkovic SF (2008) Navigating the channels and beyond: unravelling the genetics of the epilepsies. Lancet Neurol 7(3):231–245

    PubMed  Google Scholar 

  31. Heron SE, Khosravani H, Varela D, Bladen C, Williams TC, Newman MR, Scheffer IE, Berkovic SF, Mulley JC, Zamponi GW (2007) Extended spectrum of idiopathic generalized epilepsies associated with CACNA1H functional variants. Ann Neurol 62(6):560–568

    CAS  PubMed  Google Scholar 

  32. Kanyshkova T, Meuth P, Bista P, Liu Z, Ehling P, Caputi L, Doengi M, Chetkovich DM, Pape HC, Budde T (2012) Differential regulation of HCN channel isoform expression in thalamic neurons of epileptic and non-epileptic rat strains. Neurobiol Dis 45(1):450–461

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Karimzadeh F, Soleimani M, Mehdizadeh M, Jafarian M, Mohamadpour M, Kazemi H, Joghataei MT, Gorji A (2013) Diminution of the NMDA receptor NR subunit in cortical and subcortical areas of WAG/Rij rats. Synapse 67:839–846

    CAS  PubMed  Google Scholar 

  34. Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature 386(6622):239–246

    CAS  PubMed  Google Scholar 

  35. Kennard JT, Barmanray R, Sampurno S, Ozturk E, Reid CA, Paradiso L, D’Abaco GM, Kaye AH, Foote SJ, O’Brien TJ, Powell KL (2011) Stargazin and AMPA receptor membrane expression is increased in the somatosensory cortex of Genetic Absence Epilepsy Rats from Strasbourg. Neurobiol Dis 42(1):48–54

    CAS  PubMed  Google Scholar 

  36. Kharlamov EA, Lepsveridze E, Meparishvili M, Solomonia RO, Lu B, Miller ER, Kelly KM, Mtchedlishvili Z (2011) Alterations of GABA(A) and glutamate receptor subunits and heat shock protein in rat hippocampus following traumatic brain injury and in posttraumatic epilepsy. Epilepsy Res 95(1–2):20–34

    CAS  PubMed  Google Scholar 

  37. Khosravani H, Altier C, Simms B, Hamming KS, Snutch TP, Mezeyova J, McRory JE, Zamponi GW (2004) Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy. J Biol Chem 279(11):9681–9684

    CAS  PubMed  Google Scholar 

  38. Kirschstein T, Bauer M, Muller L, Ruschenschmidt C, Reitze M, Becker AJ, Schoch S, Beck H (2007) Loss of metabotropic glutamate receptor-dependent long-term depression via downregulation of mGluR5 after status epilepticus. J Neurosci 27(29):7696–7704

    CAS  PubMed  Google Scholar 

  39. Klein JP, Khera DS, Nersesyan H, Kimchi EY, Waxman SG, Blumenfeld H (2004) Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy. Brain Res 1000(1–2):102–109

    CAS  PubMed  Google Scholar 

  40. Kole MH, Brauer AU, Stuart GJ (2007) Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model. J Physiol 578(Pt 2):507–525

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Kuisle M, Wanaverbecq N, Brewster AL, Frere SG, Pinault D, Baram TZ, Luthi A (2006) Functional stabilization of weakened thalamic pacemaker channel regulation in rat absence epilepsy. J Physiol 575(Pt 1):83–100

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Lei Z, Deng P, Li J, Xu ZC (2012) Alterations of A-type potassium channels in hippocampal neurons after traumatic brain injury. J Neurotrauma 29(2):235–245

    PubMed Central  PubMed  Google Scholar 

  43. Letts VA, Felix R, Biddlecome GH, Arikkath J, Mahaffey CL, Valenzuela A, Bartlett FS 2nd, Mori Y, Campbell KP, Frankel WN (1998) The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit. Nat Genet 19(4):340–347

    CAS  PubMed  Google Scholar 

  44. Li JM, Zeng YJ, Peng F, Li L, Yang TH, Hong Z, Lei D, Chen Z, Zhou D (2010) Aberrant glutamate receptor 5 expression in temporal lobe epilepsy lesions. Brain Res 1311:166–174

    CAS  PubMed  Google Scholar 

  45. Liang J, Zhang Y, Wang J, Pan H, Wu H, Xu K, Liu X, Jiang Y, Shen Y, Wu X (2006) New variants in the CACNA1H gene identified in childhood absence epilepsy. Neurosci Lett 406(1–2):27–32

    CAS  PubMed  Google Scholar 

  46. Lie AA, Becker A, Behle K, Beck H, Malitschek B, Conn PJ, Kuhn R, Nitsch R, Plaschke M, Schramm J, Elger CE, Wiestler OD, Blumcke I (2000) Up-regulation of the metabotropic glutamate receptor mGluR4 in hippocampal neurons with reduced seizure vulnerability. Ann Neurol 47(1):26–35

    CAS  PubMed  Google Scholar 

  47. Liu XB, Coble J, van Luijtelaar G, Jones EG (2007) Reticular nucleus-specific changes in alpha3 subunit protein at GABA synapses in genetically epilepsy-prone rats. Proc Natl Acad Sci U S A 104(30):12512–12517

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Loup F, Wieser HG, Yonekawa Y, Aguzzi A, Fritschy JM (2000) Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy. J Neurosci 20(14):5401–5419

    CAS  PubMed  Google Scholar 

  49. Lukasiuk K, Dabrowski M, Adach A, Pitkanen A (2006) Epileptogenesis-related genes revisited. Prog Brain Res 158:223–241

    CAS  PubMed  Google Scholar 

  50. Macdonald RL, Olsen RW (1994) GABAA receptor channels. Annu Rev Neurosci 17:569–602

    CAS  PubMed  Google Scholar 

  51. Mantegazza M, Catterall WA (2012) Voltage-gated Na+ channels:structure, function, and pathophysiology. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds) Jasper’s basic mechanisms of the epilepsies, 4th edn. Bethesda, pp 41–54

    Google Scholar 

  52. Marescaux C, Vergnes M (1995) Genetic absence epilepsy in rats from Strasbourg (GAERS). Ital J Neurol Sci 16(1–2):113–118

    CAS  PubMed  Google Scholar 

  53. Marescaux C, Vergnes M, Depaulis A (1992) Genetic absence epilepsy in rats from Strasbourg – a review. J Neural Transm Suppl 35:37–69

    CAS  PubMed  Google Scholar 

  54. Mathern GW, Pretorius JK, Leite JP, Kornblum HI, Mendoza D, Lozada A, Bertram EH 3rd (1998) Hippocampal AMPA and NMDA mRNA levels and subunit immunoreactivity in human temporal lobe epilepsy patients and a rodent model of chronic mesial limbic epilepsy. Epilepsy Res 32(1–2):154–171

    CAS  PubMed  Google Scholar 

  55. Merlo D, Mollinari C, Inaba Y, Cardinale A, Rinaldi AM, D’Antuono M, D’Arcangelo G, Tancredi V, Ragsdale D, Avoli M (2007) Reduced GABAB receptor subunit expression and paired-pulse depression in a genetic model of absence seizures. Neurobiol Dis 25(3):631–641

    CAS  PubMed  Google Scholar 

  56. Monaghan MM, Menegola M, Vacher H, Rhodes KJ, Trimmer JS (2008) Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy. Neuroscience 156(3):550–562

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Monteggia LM, Eisch AJ, Tang MD, Kaczmarek LK, Nestler EJ (2000) Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain. Brain Res Mol Brain Res 81(1–2):129–139

    CAS  PubMed  Google Scholar 

  58. Munoz A, Arellano JI, DeFelipe J (2002) GABABR1 receptor protein expression in human mesial temporal cortex: changes in temporal lobe epilepsy. J Comp Neurol 449(2):166–179

    CAS  PubMed  Google Scholar 

  59. Ngomba RT, Ferraguti F, Badura A, Citraro R, Santolini I, Battaglia G, Bruno V, De Sarro G, Simonyi A, van Luijtelaar G, Nicoletti F (2008) Positive allosteric modulation of metabotropic glutamate 4 (mGlu4) receptors enhances spontaneous and evoked absence seizures. Neuropharmacology 54(2):344–354

    CAS  PubMed  Google Scholar 

  60. Ngomba RT, Santolini I, Biagioni F, Molinaro G, Simonyi A, van Rijn CM, D’Amore V, Mastroiacovo F, Olivieri G, Gradini R, Ferraguti F, Battaglia G, Bruno V, Puliti A, van Luijtelaar G, Nicoletti F (2011a) Protective role for type-1 metabotropic glutamate receptors against spike and wave discharges in the WAG/Rij rat model of absence epilepsy. Neuropharmacology 60(7–8):1281–1291

    CAS  Google Scholar 

  61. Ngomba RT, Santolini I, Salt TE, Ferraguti F, Battaglia G, Nicoletti F, van Luijtelaar G (2011b) Metabotropic glutamate receptors in the thalamocortical network: strategic targets for the treatment of absence epilepsy. Epilepsia 52(7):1211–1222

    CAS  Google Scholar 

  62. Pacheco Otalora LF, Couoh J, Shigamoto R, Zarei MM, Garrido Sanabria ER (2006) Abnormal mGluR2/3 expression in the perforant path termination zones and mossy fibers of chronically epileptic rats. Brain Res 1098(1):170–185

    CAS  PubMed  Google Scholar 

  63. Pape HC (1996) Queer current and pacemaker: the hyperpolarization-activated cation current in neurons. Annu Rev Physiol 58:299–327

    CAS  PubMed  Google Scholar 

  64. Peloquin JB, Khosravani H, Barr W, Bladen C, Evans R, Mezeyova J, Parker D, Snutch TP, McRory JE, Zamponi GW (2006) Functional analysis of Ca3.2 T-type calcium channel mutations linked to childhood absence epilepsy. Epilepsia 47(3):655–658

    PubMed  Google Scholar 

  65. Peng Z, Huang CS, Stell BM, Mody I, Houser CR (2004) Altered expression of the delta subunit of the GABAA receptor in a mouse model of temporal lobe epilepsy. J Neurosci 24(39):8629–8639

    CAS  PubMed  Google Scholar 

  66. Penschuck S, Bastlund JF, Jensen HS, Stensbol TB, Egebjerg J, Watson WP (2005) Changes in KCNQ2 immunoreactivity in the amygdala in two rat models of temporal lobe epilepsy. Brain Res Mol Brain Res 141(1):66–73

    CAS  PubMed  Google Scholar 

  67. Perez-Reyes E (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 83(1):117–161

    CAS  PubMed  Google Scholar 

  68. Pinault D, O’Brien TJ (2007) Cellular and network mechanisms of genetically-determined absence seizures. Thalamus Relat Syst 3:181–203

    PubMed Central  Google Scholar 

  69. Pirker S, Schwarzer C, Czech T, Baumgartner C, Pockberger H, Maier H, Hauer B, Sieghart W, Furtinger S, Sperk G (2003) Increased expression of GABA(A) receptor beta-subunits in the hippocampus of patients with temporal lobe epilepsy. J Neuropathol Exp Neurol 62(8):820–834

    CAS  PubMed  Google Scholar 

  70. Pisu MG, Mostallino MC, Dore R, Mura ML, Maciocco E, Russo E, De Sarro G, Serra M (2008) Neuroactive steroids and GABAA receptor plasticity in the brain of the WAG/Rij rat, a model of absence epilepsy. J Neurochem 106(6):2502–2514

    CAS  PubMed  Google Scholar 

  71. Pitkanen A, Lukasiuk K (2009) Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy Behav 14(Suppl 1):16–25

    PubMed  Google Scholar 

  72. Pitkanen A, Lukasiuk K (2011) Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 10(2):173–186

    PubMed  Google Scholar 

  73. Powell KL, Cain SM, Snutch TP, O’Brien TJ (2013) Low threshold T-type calcium channels as targets for novel epilepsy treatments. Br J Clin Pharmacol. doi:10.1111/bcp.12205

  74. Princivalle AP, Richards DA, Duncan JS, Spreafico R, Bowery NG (2003) Modification of GABA(B1) and GABA(B2) receptor subunits in the somatosensory cerebral cortex and thalamus of rats with absence seizures (GAERS). Epilepsy Res 55(1–2):39–51

    CAS  PubMed  Google Scholar 

  75. Raible DJ, Frey LC, Cruz Del Angel Y, Russek SJ, Brooks-Kayal AR (2012) GABA(A) receptor regulation after experimental traumatic brain injury. J Neurotrauma 29(16):2548–2554

    PubMed Central  PubMed  Google Scholar 

  76. Reid CA, Phillips AM, Petrou S (2012) HCN channelopathies: pathophysiology in genetic epilepsy and therapeutic implications. Br J Pharmacol 165(1):49–56

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Remy S, Gabriel S, Urban BW, Dietrich D, Lehmann TN, Elger CE, Heinemann U, Beck H (2003) A novel mechanism underlying drug resistance in chronic epilepsy. Ann Neurol 53(4):469–479

    CAS  PubMed  Google Scholar 

  78. Rohde J, Kirschstein T, Wilkars W, Muller L, Tokay T, Porath K, Bender RA, Kohling R (2012) Upregulation of presynaptic mGluR2, but not mGluR3 in the epileptic medial perforant path. Neuropharmacology 62(4):1867–1873

    CAS  PubMed  Google Scholar 

  79. Santoro B, Tibbs GR (1999) The HCN gene family: molecular basis of the hyperpolarization-activated pacemaker channels. Ann N Y Acad Sci 868:741–764

    CAS  PubMed  Google Scholar 

  80. Schwartzkroin PA (2012) Cellular bases of focal and generalized epilepsies. Handb Clin Neurol 107:13–33

    PubMed  Google Scholar 

  81. Schwarzer C, Tsunashima K, Wanzenbock C, Fuchs K, Sieghart W, Sperk G (1997) GABA(A) receptor subunits in the rat hippocampus II: altered distribution in kainic acid-induced temporal lobe epilepsy. Neuroscience 80(4):1001–1017

    CAS  PubMed  Google Scholar 

  82. Shin M, Brager D, Jaramillo TC, Johnston D, Chetkovich DM (2008) Mislocalization of h channel subunits underlies h channelopathy in temporal lobe epilepsy. Neurobiol Dis 32(1):26–36

    PubMed Central  PubMed  Google Scholar 

  83. Solomonia R, Mikautadze E, Nozadze M, Kuchiashvili N, Lepsveridze E, Kiguradze T (2010) Myo-inositol treatment prevents biochemical changes triggered by kainate-induced status epilepticus. Neurosci Lett 468(3):277–281

    CAS  PubMed  Google Scholar 

  84. Sperk G, Schwarzer C, Tsunashima K, Fuchs K, Sieghart W (1997) GABA(A) receptor subunits in the rat hippocampus I: immunocytochemical distribution of 13 subunits. Neuroscience 80(4):987–1000

    CAS  PubMed  Google Scholar 

  85. Sperk G, Schwarzer C, Tsunashima K, Kandlhofer S (1998) Expression of GABA(A) receptor subunits in the hippocampus of the rat after kainic acid-induced seizures. Epilepsy Res 32(1–2):129–139

    CAS  PubMed  Google Scholar 

  86. Spreafico R, Mennini T, Danober L, Cagnotto A, Regondi MC, Miari A, De Blas A, Vergnes M, Avanzini G (1993) GABAA receptor impairment in the genetic absence epilepsy rats from Strasbourg (GAERS): an immunocytochemical and receptor binding autoradiographic study. Epilepsy Res 15(3):229–238

    CAS  PubMed  Google Scholar 

  87. Stewart LS, Wu Y, Eubanks JH, Han H, Leschenko Y, Perez Velazquez JL, Cortez MA, Snead OC 3rd (2009) Severity of atypical absence phenotype in GABAB transgenic mice is subunit specific. Epilepsy Behav 14(4):577–581

    PubMed  Google Scholar 

  88. Straessle A, Loup F, Arabadzisz D, Ohning GV, Fritschy JM (2003) Rapid and long-term alterations of hippocampal GABAB receptors in a mouse model of temporal lobe epilepsy. Eur J Neurosci 18(8):2213–2226

    PubMed  Google Scholar 

  89. Strauss U, Kole MH, Brauer AU, Pahnke J, Bajorat R, Rolfs A, Nitsch R, Deisz RA (2004) An impaired neocortical Ih is associated with enhanced excitability and absence epilepsy. Eur J Neurosci 19(11):3048–3058

    PubMed  Google Scholar 

  90. Su T, Cong WD, Long YS, Luo AH, Sun WW, Deng WY, Liao WP (2008) Altered expression of voltage-gated potassium channel 4.2 and voltage-gated potassium channel 4-interacting protein, and changes in intracellular calcium levels following lithium-pilocarpine-induced status epilepticus. Neuroscience 157(3):566–576

    CAS  PubMed  Google Scholar 

  91. Sun C, Mtchedlishvili Z, Erisir A, Kapur J (2007) Diminished neurosteroid sensitivity of synaptic inhibition and altered location of the alpha4 subunit of GABA(A) receptors in an animal model of epilepsy. J Neurosci 27(46):12641–12650

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Sun QJ, Duan RS, Wang AH, Shang W, Zhang T, Zhang XQ, Chi ZF (2009) Alterations of NR2B and PSD-95 expression in hippocampus of kainic acid-exposed rats with behavioural deficits. Behav Brain Res 201(2):292–299

    CAS  PubMed  Google Scholar 

  93. Talley EM, Solorzano G, Depaulis A, Perez-Reyes E, Bayliss DA (2000) Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat. Brain Res Mol Brain Res 75(1):159–165

    CAS  PubMed  Google Scholar 

  94. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62(3):405–496

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Tsakiridou E, Bertollini L, de Curtis M, Avanzini G, Pape HC (1995) Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy. J Neurosci 15(4):3110–3117

    CAS  PubMed  Google Scholar 

  96. Ulas J, Satou T, Ivins KJ, Kesslak JP, Cotman CW, Balazs R (2000) Expression of metabotropic glutamate receptor 5 is increased in astrocytes after kainate-induced epileptic seizures. Glia 30(4):352–361

    CAS  PubMed  Google Scholar 

  97. Ullal G, Fahnestock M, Racine R (2005) Time-dependent effect of kainate-induced seizures on glutamate receptor GluR5, GluR6, and GluR7 mRNA and protein expression in rat hippocampus. Epilepsia 46(5):616–623

    CAS  PubMed  Google Scholar 

  98. van de Bovenkamp-Janssen MC, van der Kloet JC, van Luijtelaar G, Roubos EW (2006) NMDA-NR1 and AMPA-GluR4 receptor subunit immunoreactivities in the absence epileptic WAG/Rij rat. Epilepsy Res 69(2):119–128

    PubMed  Google Scholar 

  99. van Gassen KL, de Wit M, van Kempen M, van der Hel WS, van Rijen PC, Jackson AP, Lindhout D, de Graan PN (2009) Hippocampal Nabeta3 expression in patients with temporal lobe epilepsy. Epilepsia 50(4):957–962

    PubMed  Google Scholar 

  100. Vitko I, Chen Y, Arias JM, Shen Y, Wu XR, Perez-Reyes E (2005) Functional characterization and neuronal modeling of the effects of childhood absence epilepsy variants of CACNA1H, a T-type calcium channel. J Neurosci 25(19):4844–4855

    CAS  PubMed  Google Scholar 

  101. Wainger BJ, DeGennaro M, Santoro B, Siegelbaum SA, Tibbs GR (2001) Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature 411(6839):805–810

    CAS  PubMed  Google Scholar 

  102. Winden KD, Karsten SL, Bragin A, Kudo LC, Gehman L, Ruidera J, Geschwind DH, Engel J Jr (2011) A systems level, functional genomics analysis of chronic epilepsy. PLoS One 6(6):e20763

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Wu Y, Chan KF, Eubanks JH, Guin Ting Wong C, Cortez MA, Shen L, Che Liu C, Perez Velazquez J, Tian Wang Y, Jia Z, Carter Snead O 3rd (2007) Transgenic mice over-expressing GABA(B)R1a receptors acquire an atypical absence epilepsy-like phenotype. Neurobiol Dis 26(2):439–451

    CAS  PubMed  Google Scholar 

  104. Yalcin O (2012) Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies. Seizure 21(2):79–86

    PubMed  Google Scholar 

  105. Zhang N, Wei W, Mody I, Houser CR (2007) Altered localization of GABA(A) receptor subunits on dentate granule cell dendrites influences tonic and phasic inhibition in a mouse model of epilepsy. J Neurosci 27(28):7520–7531

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by a Polish Ministry of Science and Education grant DNP/N119/ESF-EuroEPINOMICS/2012 to K.L. and the Academy of Finland, the Sigrid Juselius Foundation, CURE grant to A.P.

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Authors and Affiliations

  1. Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, 4th Floor Clinical Sciences Building, Royal Parade, Parkville, 3050, VIC, Australia

    Kim L. Powell & Terence J. O’Brien

  2. The Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St, 02 093, Warsaw, Poland

    Katarzyna Lukasiuk

  3. Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 1627, FIN-70 211, Kuopio, Finland

    Asla Pitkänen M.D., Ph.D.

  4. Department of Neurology, Kuopio University Hospital, Kuopio, Finland

    Asla Pitkänen M.D., Ph.D.

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  1. Kim L. Powell
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  2. Katarzyna Lukasiuk
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  3. Terence J. O’Brien
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  4. Asla Pitkänen M.D., Ph.D.
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Correspondence to Terence J. O’Brien or Asla Pitkänen M.D., Ph.D. .

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Editors and Affiliations

  1. Dept. of Child & Adoles. Psych., Phys. & Neurosc., and Psych., New York Univ. Langone Med. Ctr., Orangeburg, New York, USA

    Helen E. Scharfman

  2. Dept. of Comp. Med. and Neurol. & Neurol. Scs., Stanford University, Stanford, California, USA

    Paul S. Buckmaster

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Powell, K.L., Lukasiuk, K., O’Brien, T.J., Pitkänen, A. (2014). Are Alterations in Transmitter Receptor and Ion Channel Expression Responsible for Epilepsies?. In: Scharfman, H., Buckmaster, P. (eds) Issues in Clinical Epileptology: A View from the Bench. Advances in Experimental Medicine and Biology, vol 813. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8914-1_17

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  • DOI: https://doi.org/10.1007/978-94-017-8914-1_17

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