Ion channel variation causes epilepsies

Article Article scientifique Revue de la littérature Ion channel variation causes epilepsies eng 2001-10 author Moulard Bruno 117703 author Picard Fabienne 123049 author Le Hellard Stéphanie 110891 author Agulhon Cendra 112615 author Weiland Sigrid 129453 author Favre Isabelle 133588 author Bertrand Sonia 23091 author Malafosse Alain 111681 author Bertrand Daniel 24727 275-284 10.1016/s0165-0173(01)00104-7 11690625 0165-0173 https://www.sciencedirect.com/science/article/pii/S0165017301001047 The discovery of genetically transmissible form of epilepsy associated with a mutation in a gene that codes for a subunit of a ligand-gated channel shined a new light in this field of neurological diseases. Because this gene (CHRNA4) codes for a neuronal nicotinic acetylcholine receptor subunit, functional studies could be designed to evaluate the alterations caused by this mutation. Since this initial observation, five mutations were identified and determination of their functional properties initiated. These experiments were extended to pairwise expression of the control and mutated allele to mimic the heterozygote human genotype. The first common functional trait identified so far, in four of these mutants, is an increased sensitivity to the acetylcholine, suggesting that these mutations may cause a gain of function. An alternative possibility that cannot be excluded is that conditions in the brain are such that these higher responding receptors may be more prone to desensitization. The importance of ionic channels as cause of epilepsies was further demonstrated with the identification of the association between the benign neonatal epilepsy and mutations in genes coding for potassium channel subunits (KCNQ2, KCNQ3). Additional evidences were brought by the identification of mutations in voltage-dependent sodium channels (SCN1A, SCN1B) in a form of generalized epilepsy with febrile seizures. Acetylcholine / genetics Acetylcholine / metabolism Animals Brain / metabolism Brain / pathology Brain / physiopathology Brain Chemistry / genetics Epilepsy / genetics Epilepsy / metabolism Epilepsy / physiopathology Gene Expression Regulation / genetics Humans Ion Channels / genetics Ion Channels / metabolism Mutation / genetics Receptors, Nicotinic / genetics Receptors, Nicotinic / metabolism Synaptic Transmission / genetics Dewey 616.89 Dewey 612 134 Département de physiologie cellulaire et métabolisme 21C 60 Département de psychiatrie 225 false Brain research reviews 36 2-3 342e1a15-50c6-45fb-a8fd-3ba038da8bd0 Article (Published version) Restricted 1-s2.0-S0165017301001047-main.pdf 1359997 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Ion channel variation causes epilepsies	Brain research reviews			2001	135	0

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