Properties of mutated murine alpha4beta2 nicotinic receptors linked to partial epilepsy.
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.
Lipovsek
Marcela
M
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina.
Plazas
Paola
P
Savino
Jessica
J
Klaassen
Alwin
A
Boulter
Jim
J
Elgoyhen
Ana Belén
AB
Katz
Eleonora
E
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
D018678:Cholinergic Agents; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine