The sensitivity of AMPA-selective glutamate receptor channels to pentobarbital is determined by a single amino acid residue of the alpha 2 subunit.
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.
Yamakura
T
T
Department of Molecular Neurobiology, Niigata University, Japan.
Sakimura
K
K
Mishina
M
M
Shimoji
K
K
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
D007473:Ion Channels; D018091:Receptors, AMPA; D005973:Glutamine; D001120:Arginine; D010424:Pentobarbital