title: Properties of mutated murine alpha4beta2 nicotinic receptors linked to partial epilepsy.
abstract: We characterized, by electrophysiological methods, two biophysical properties of murine recombinant alpha4beta2 nicotinic acetylcholine receptors (nAChR) bearing a mutation (alpha4:+L264alpha4:beta2 or alpha4:S252Falpha4:beta2) linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to acetylcholine (ACh) was increased by the S252F substitution expressed in heterozygosis (alpha4:S252Falpha4:beta2) but was markedly reduced when this mutation was expressed in homozygosis (S252Falpha4:beta2). ACh sensitivity was not altered by the +L264 insertion. Moreover, receptor desensitization was significantly increased by both mutations expressed in heterozygosis. These results are in general agreement to those of rat and human recombinant receptors bearing the same mutations, thus contributing to validate the use of knock-in mice harboring ADNFLE mutations as models to study this pathology.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Lipovsek
authors.forename: Paola
authors.initials: P
authors.lastname: Plazas
authors.forename: Jessica
authors.initials: J
authors.lastname: Savino
authors.forename: Alwin
authors.initials: A
authors.lastname: Klaassen
authors.forename: Jim
authors.initials: J
authors.lastname: Boulter
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Elgoyhen
authors.forename: Eleonora
authors.initials: E
authors.lastname: Katz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology; D004828:Epilepsies, Partial / Q000235:genetics* / Q000503:physiopathology*; D005799:Genes, Dominant; D006579:Heterozygote; D006720:Homozygote; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008956:Models, Chemical; D016296:Mutagenesis; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D014981:Xenopus
chemical_list: D018678:Cholinergic Agents; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine