Gamma-aminobutyric acid receptor subunit alpha-1 explained

Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the GABRA1 gene.^[1]

GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified.^[2]

The GABRA1 receptor is the specific target of the z-drug class of nonbenzodiazepine hypnotic agents and is responsible for their hypnotic and hallucinogenic effects.

See also

• GABA_A receptor

Further reading

• Schofield PR, Pritchett DB, Sontheimer H, etal . Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits. . FEBS Lett. . 244 . 2 . 361–364 . 1989 . 2465923 . 10.1016/0014-5793(89)80563-0 . 84068989 . free . 1989FEBSL.244..361S .
• Garrett KM, Duman RS, Saito N, etal . Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor. . Biochem. Biophys. Res. Commun. . 156 . 2 . 1039–1045 . 1988 . 2847710 . 10.1016/S0006-291X(88)80949-5 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–174 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Kang I, Lindquist DG, Kinane TB, etal . Isolation and characterization of the promoter of the human GABAA receptor alpha 1 subunit gene. . J. Neurochem. . 62 . 4 . 1643–1646 . 1994 . 8133292 . 10.1046/j.1471-4159.1994.62041643.x . 84579971 .
• Tögel M, Mossier B, Fuchs K, Sieghart W . gamma-Aminobutyric acidA receptors displaying association of gamma 3-subunits with beta 2/3 and different alpha-subunits exhibit unique pharmacological properties. . J. Biol. Chem. . 269 . 17 . 12993–12998 . 1994 . 10.1016/S0021-9258(18)99974-6 . 8175718 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–156 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Huang RQ, Dillon GH . Maintenance of recombinant type A gamma-aminobutyric acid receptor function: role of protein tyrosine phosphorylation and calcineurin. . J. Pharmacol. Exp. Ther. . 286 . 1 . 243–255 . 1998 . 9655866 .
• Serretti A, Macciardi F, Cusin C, etal . No interaction of GABA(A) alpha-1 subunit and dopamine receptor D4 exon 3 genes in symptomatology of major psychoses. . Am. J. Med. Genet. . 88 . 1 . 44–49 . 1999 . 10050966 . 10.1002/(SICI)1096-8628(19990205)88:1<44::AID-AJMG8>3.0.CO;2-Y .
• Bonnert TP, McKernan RM, Farrar S, etal . theta, a novel gamma-aminobutyric acid type A receptor subunit. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 17 . 9891–9896 . 1999 . 10449790 . 10.1073/pnas.96.17.9891 . 22306. 1999PNAS...96.9891B . free .
• Serretti A, Lilli R, Lorenzi C, etal . Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders. . Psychiatry Research . 87 . 1 . 7–19 . 1999 . 10512150 . 10.1016/S0165-1781(99)00056-6 . 26980087 .
• Cossette P, Liu L, Brisebois K, etal . Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. . Nat. Genet. . 31 . 2 . 184–189 . 2002 . 11992121 . 10.1038/ng885 . 11974933 .
• Kumar S, Sieghart W, Morrow AL . Association of protein kinase C with GABA(A) receptors containing alpha1 and alpha4 subunits in the cerebral cortex: selective effects of chronic ethanol consumption. . J. Neurochem. . 82 . 1 . 110–117 . 2002 . 12091471 . 10.1046/j.1471-4159.2002.00943.x . 82745932 .
• Trudell J . Unique assignment of inter-subunit association in GABA(A) alpha 1 beta 3 gamma 2 receptors determined by molecular modeling. . Biochim. Biophys. Acta . 1565 . 1 . 91–96 . 2002 . 12225856 . 10.1016/S0005-2736(02)00512-6 . free .
• Sarto I, Wabnegger L, Dögl E, Sieghart W . Homologous sites of GABA(A) receptor alpha(1), beta(3) and gamma(2) subunits are important for assembly. . Neuropharmacology . 43 . 4 . 482–491 . 2002 . 12367595 . 10.1016/S0028-3908(02)00160-0 . 140209788 .
• Jenkins A, Andreasen A, Trudell JR, Harrison NL . Tryptophan scanning mutagenesis in TM4 of the GABA(A) receptor alpha1 subunit: implications for modulation by inhaled anesthetics and ion channel structure. . Neuropharmacology . 43 . 4 . 669–678 . 2002 . 12367612 . 10.1016/S0028-3908(02)00175-2 . 41156918 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . free .
• Kash TL, Jenkins A, Kelley JC, etal . Coupling of agonist binding to channel gating in the GABA(A) receptor. . Nature . 421 . 6920 . 272–275 . 2003 . 12529644 . 10.1038/nature01280 . 2003Natur.421..272K . 4429883 .
• Lin SK, Chen CK, Ball D, etal . Gender-specific contribution of the GABA(A) subunit genes on 5q33 in methamphetamine use disorder. . Pharmacogenomics J. . 3 . 6 . 349–355 . 2004 . 14569258 . 10.1038/sj.tpj.6500203 . 177019 .
• Mercik K, Pytel M, Mozrzymas JW . Recombinant alpha 1 beta 2 gamma 2 GABA(A) receptors expressed in HEK293 and in QT6 cells show different kinetics. . Neurosci. Lett. . 352 . 3 . 195–198 . 2004 . 14625018 . 10.1016/j.neulet.2003.08.060 . 53298392 .

Notes and References

1. Johnson KJ, Sander T, Hicks AA, van Marle A, Janz D, Mullan MJ, Riley BP, Darlison MG . Confirmation of the localization of the human GABAA receptor alpha 1-subunit gene (GABRA1) to distal 5q by linkage analysis . Genomics . 14 . 3 . 745–748 . Dec 1992 . 1330891 . 10.1016/S0888-7543(05)80178-8.
2. Web site: Entrez Gene: GABRA1 gamma-aminobutyric acid (GABA) A receptor, alpha 1.