title: The sensitivity of AMPA-selective glutamate receptor channels to pentobarbital is determined by a single amino acid residue of the alpha 2 subunit.
abstract: Clinical concentrations of pentobarbital inhibit the alpha-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor (GluR) channels. Recently, the AMPA-selective GluR channels that contained the alpha 2 subunit were shown to be more sensitive to pentobarbital block than those without the alpha 2 subunit. Here we demonstrated that replacement by glutamine of the arginine residue in putative transmembrane segment M2 of the alpha 2 subunit (mutation alpha 2-R586Q) drastically reduced the pentobarbital sensitivity of the alpha 2 heteromeric channel to the level comparable to those of the alpha 1 and alpha 2-R586Q homomeric channels. These results suggest that the arginine residue in segment M2 of the alpha 2 subunit is the critical determinant of the sensitivities of the AMPA-selective GluR channels to pentobarbital.
authors.affiliation: Department of Molecular Neurobiology, Niigata University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamakura
authors.forename: K
authors.initials: K
authors.lastname: Sakimura
authors.forename: M
authors.initials: M
authors.lastname: Mishina
authors.forename: K
authors.initials: K
authors.lastname: Shimoji
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry*; D004553:Electric Conductivity; D005973:Glutamine / Q000737:chemistry; D007473:Ion Channels / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010424:Pentobarbital / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D007473:Ion Channels; D018091:Receptors, AMPA; D005973:Glutamine; D001120:Arginine; D010424:Pentobarbital