title: Properties of a novel GABAA receptor γ2 subunit mutation associated with seizures.
abstract: We recently identified a novel missense mutation of the γ(2) subunit at position 40 with serine (N40S) of the GABA(A) receptor from a patient with epilepsy. Here, we report properties of the mutant receptor using the whole cell patch clamp technique. The Hill coefficient for the N40S receptor was greater than for the wild-type (WT) receptor, while the EC50 and kinetics did not differ. Furthermore, the effects of diazepam, Zn(2+), bicuculline, and pH were indistinguishable between WT and N40S receptors. These results suggest that the changes in the steepness of the concentration-response relationship for GABA in the N40S receptor may trigger epilepsy.
authors.affiliation: Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Migita
authors.forename: Junko
authors.initials: J
authors.lastname: Yamada
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nikaido
authors.forename: XiuYu
authors.initials: X
authors.lastname: Shi
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueno
mesh_terms: D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A