Title: Properties of mutated murine alpha4beta2 nicotinic receptors linked to partial epilepsy

MARCELA LIPOVSEK; PAOLA V. PLAZAS; ALWIN KLAASEN; JIM BOULTER; ANA BELÉN ELGOYHEN; ELEONORA KATZ

NEUROSCIENCE LETTERS

ELSEVIER IRELAND LTD

Año: 2008 vol. 434 p. 165 - 169

0304-3940

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 markedlyreduced 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 thoseof rat and human recombinant receptors bearing the same mutations, thus contributing to validate the use of knock-in mice harboring ADNFLEmutations as models to study this pathology.