Properties of mutated murine α4β2 nicotinic receptors linked to partial epilepsy

• Published in: Neuroscience letters 2008-03, Vol.434 (2), p.165-169
• Main Authors: Lipovsek, Marcela, Plazas, Paola, Savino, Jessica, Klaassen, Alwin, Boulter, Jim, Elgoyhen, Ana Belén, Katz, Eleonora
• Format: Article
• Language: English
• Subjects: ACh; Biological and medical sciences; Desensitization; Epilepsy; Fundamental and applied biological sciences. Psychology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Ion channels; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Nicotinic receptors; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2007.12.061

We characterized, by electrophysiological methods, two biophysical properties of murine recombinant α4β2 nicotinic acetylcholine receptors (nAChR) bearing a mutation (α4:+L264α4:β2 or α4:S252Fα4:β2) linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to acetylcholine (ACh) was increased by the S252F substitution expressed in heterozygosis (α4:S252Fα4:β2) but was markedly reduced when this mutation was expressed in homozygosis (S252Fα4:β2). 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.