Properties of mutated murine alpha4beta2 nicotinic receptors linked to partial epilepsy.

TitleProperties of mutated murine alpha4beta2 nicotinic receptors linked to partial epilepsy.
Publication TypeJournal Article
Year of Publication2008
AuthorsLipovsek, M, Plazas P, Savino J, Klaassen A, Boulter J, Elgoyhen AB, Katz E
JournalNeuroscience letters
Volume434
Issue2
Pagination165-9
Date Published2008 Mar 28
ISSN0304-3940
Keywordsacetylcholine, Animals, Cholinergic Agents, Epilepsies, Partial, Genes, Dominant, Heterozygote, Homozygote, Ion Channel Gating, Mice, Models, Chemical, Mutagenesis, Oocytes, Patch-Clamp Techniques, Receptors, Nicotinic, Xenopus
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.

Alternate JournalNeurosci. Lett.