Epileptogenic Channelopathies

  • Giuliano Avanzini
Reference work entry


A first evidence of the great potential of the synergy between genetics, molecular biology, and neurophysiology for understanding the pathophysiology of depending on mutations of ion channel genes was provided by the work of the Jan (Jan et al. 1977; Timpe et al. 1988) on the fly Drosophila Melnogaster ( Fig. 20-1). The implications of genetically determined channel dysfunctions in different paroxysmal muscular and cardiac disorders have been increasingly acknowledged since the 1991 publication of the seminal paper by Ptaceck et al. ( 1991) concerning hyperkalemic periodic paralysis that established the concept of channelopathy. According to Ptaceck ( 1997), the term channelopathy designates genetically determined ion channel alterations that lead to acute and transient symptoms in subjects who otherwise seem to be perfectly normal. This definition fits idiopathic epilepsies, which are considered to depend on primary dysfunction of ion channels responsible for membrane...


Xenopus Oocyte Febrile Seizure Idiopathic Epilepsy Frontal Lobe Epilepsy Dravet Syndrome 
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  1. Avanzini G, Franceschetti S, Mantegazza M (2007) Epileptogenic channelopathies: experimental models of human pathologies. Epilepsia 48(Suppl 2):51–64CrossRefPubMedGoogle Scholar
  2. Avanzini G, Ptàcek LJ (2002) Epilepsies as channelopathies. In: Guerrini R, Aicardi J, Andermann F, Hallett M (eds) Epilepsy and movement disorders. Cambridge University Press, Cambridge, pp 1–14Google Scholar
  3. Barnard EA, Miledi R, Sumikawa K (1982) Translation of exogenous messenger RNA coding for nicotinic acetylcholine receptors produces functional receptors in Xenopus oocytes. Proc R Soc Lond B Biol Sci 215:241–246CrossRefPubMedGoogle Scholar
  4. Baulac S et al. (2001) First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the γ2-subunit gene. Nature Genet 28:46–48CrossRefPubMedGoogle Scholar
  5. Burgess DL, Noebels JL (1999) Single gene defects in mice: the role of voltagedependent calcium channels in absence models. Epilepsy Res 36:111–122CrossRefPubMedGoogle Scholar
  6. Charlier C et al. (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nature Genet 18:53–55CrossRefPubMedGoogle Scholar
  7. Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P (2001) De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 68(6):327–332CrossRefGoogle Scholar
  8. Fletcher CF, Frankel WN (1999) Ataxic mouse mutants and molecular mechanisms of absence epilepsy. Hum Mol Genet 8:1907–1912CrossRefPubMedGoogle Scholar
  9. Jan YN, Jan YL, Dennis MJ (1977) Two mutations of synaptic transmission in Drosophila. Proc R Soc London Ser B 198:87–108CrossRefGoogle Scholar
  10. Lossin C, Wang DW, Rhodes TH, Vanoye CG, George AL Jr (2002) Molecular basis of an inherited epilepsy. Neuron 34:877–884CrossRefPubMedGoogle Scholar
  11. Ptaceck LJ (1997) Channelopathies: ion channel disorders of muscle as a paradigm for paroxysmal disorders of the nervous system. Neuromusc Disord 7:250–255CrossRefGoogle Scholar
  12. Ptaceck LJ, George AL, Griggs RC, Tawil R, Kallen RG, Barchi RL, Robertson M, Leppert MF (1991) Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell 67:1021–1027CrossRefGoogle Scholar
  13. Singh NA et al. (1998) A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nature Genet 18:25–29CrossRefPubMedGoogle Scholar
  14. Steinlein O et al. (1995) A missense mutation in the neuronal nicotinic acetylcholine receptor α4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nature Genet 11:201–203CrossRefPubMedGoogle Scholar
  15. Timpe LC, Schwarz TL, Temple BL, Papazian BM, Jan YN, Jan LY (1988) Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes. Nature 331:143–145CrossRefPubMedGoogle Scholar
  16. Wallace RH, Wang DW, Singh R, Scheffer IE, George AL Jr, Phillips HA, Saar K, Reis A, Johnson EW, Sutherland GR, Berkovic SF, Mulley JC (1998) Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet 19:366–370CrossRefPubMedGoogle Scholar
  17. Yu FH, Mantegazza M, Westenbroek RE, Robbins CA, Kalume F, Burton KA, Spain WJ, McKnight GS, Scheuer T, Catterall WA (2006) Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsyè in infancy. Nat Neurosci 9:1142–1149CrossRefPubMedGoogle Scholar

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© Springer-Verlag London Limited 2010

Authors and Affiliations

  • Giuliano Avanzini
    • 1
  1. 1.Istituto Nazionale Neurologico “C.Besta”MilanItaly

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