A structural determinant of desensitization and allosteric regulation by pentobarbitone of the GABAA receptor.
Functional properties of the alpha1beta1 GABAA receptor changes in a subunit-specific manner when a threonine residue in the M2 region at the 12' position was mutated to glutamine. The rate and extent of desensitization increased in all mutants but the rate of activation was faster in the beta1 mutants. A negligible plateau current and abolition of potentiation by pentobarbitone of the GABA-activated current depended on the Thr 12' Gln mutation being present in the beta1 subunit. The Hill coefficient of the peak current response to GABA was reduced to less than one also in a beta1 subunit-specific manner. It was concluded that the beta1 subunit dominated conformational changes activated by GABA.
Birnir
B
B
Membrane Biology Program, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Tierney
M L
ML
Dalziel
J E
JE
Cox
G B
GB
Gage
P W
PW
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D016367:Baculoviridae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology*; D018079:Receptors, GABA / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital