Properties of mutated murine a4b2 nicotinic receptors

LIPOVSEK M; SAVINO J; KLAASSEN; BOULTER J; ELGOYHEN AB; KATZ E

NEUROSCIENCE LETTERS

Elsevier

Año: 2008 vol. 434 p. 165 - 169

0304-3940

We characterized, by electrophysiological methods, two biophysical properties of murine recombinant a4b2 nicotinic acetylcholine receptors (nAChR) bearing a mutation (a4:+L264a4:b2 or a4:S252Fa4:b2) linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to acetylcholine (ACh) was increased by the S252F substitution expressed in heterozygosis (a4:S252Fa4:b2) but was markedly reduced when this mutation was expressed in homozygosis (S252Fa4:b2). 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.