GABR heteropentamers:GABA transport Cl- from extracellular region to cytosol

Stable Identifier
Reaction [transition]
Homo sapiens
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The GABA(A) receptor (GABR) family belongs to the ligand-gated ion channel superfamily (LGIC). Its endogenous ligand is gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. There are six alpha subunits (GABRA) (Garrett et al. 1988, Schofield et al. 1989, Hadingham et al. 1993, Edenberg et al. 2004, Hadingham et al. 1993, Yang et al. 1995, Wingrove et al. 1992, Hadingham et al. 1996), three beta subunits (GABRB) (Schofield et al. 1989, Hadingham et al. 1993, Wagstaff et al. 1991), 2 gamma subunits (GABRG) (Khan et al. 1993, Hadingham et al. 1995) and a theta subunit (Bonnert et al. 1999) characterised to date. GABA(A) functions as a heteropentamer, the most common structure being 2 alpha subunits, 2 beta subunits and a gamma subunit (2GABRA:2GABRB:GABRG). An alternative heteropentamer with much less affinity for GABA is 2GABRA:GABRB:GABRG:GABRQ (Bonnert et al. 1999). Upon binding of GABA, both GABR complexes conduct chloride ions through their pore, resulting in hyperpolarisation of the neuron. This causes an inhibitory effect on neurotransmission by reducing the chances of a successful action potential occurring.
Literature References
PubMed ID Title Journal Year
8719416 Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site

Lan, NC, Yang, W, Drewe, JA

Eur J Pharmacol 1995
8391122 Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors

Wingrove, P, Ragan, CI, Palmer, KJ, Hadingham, KL, Whiting, PJ, Le Bourdelles, B

Mol Pharmacol 1993
8264558 Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors

Kemp, JA, Bain, C, Wingrove, PB, Ragan, CI, Palmer, KJ, Wafford, KA, Hadingham, KL, Sikela, JM, Wilcox, AS, Wilson, AW

Mol Pharmacol 1993
19828786 Extrasynaptic GABAA receptors: form, pharmacology, and function

Cope, DW, Maguire, J, Harrison, NL, Belelli, D, Walker, MC, Macdonald, RL

J Neurosci 2009
8719414 Expression and pharmacology of human GABAA receptors containing gamma 3 subunits

Palmer, KJ, Wafford, KA, Hadingham, KL, Whiting, PJ, Thompson, SA

Eur J Pharmacol 1995
17364682 GABAA receptors: properties and trafficking

Michels, G, Moss, SJ

Crit Rev Biochem Mol Biol 2007
8632757 Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors

Bain, C, Heavens, RP, Sirinathsinghji, DJ, Garrett, EM, Wafford, KA, Hadingham, KL, Whiting, PJ

Mol Pharmacol 1996
18382465 GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition

Moss, SJ, Jacob, TC, Jurd, R

Nat Rev Neurosci 2008
2847710 Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor

Duman, RS, Tallman, JF, Blume, AJ, Saito, N, Garrett, KM, Vitek, MP

Biochem Biophys Res Commun 1988
8382267 Antibodies to the human gamma 2 subunit of the gamma-aminobutyric acidA/benzodiazepine receptor

Fernando, LP, Mallet, J, Busquets, X, Khan, ZU, De Blas, AL, Filla, M, Escribá, P, Miralles, CP

J Neurochem 1993
10449790 theta, a novel gamma-aminobutyric acid type A receptor subunit

Whiting, PJ, Bonnert, TP, Heavens, RP, le Bourdellès, B, Farrar, S, McKernan, RM, Hewson, L, Rigby, MR, Wafford, KA, Sirinathsinghji, DJ, Smith, DW, Brown, N

Proc. Natl. Acad. Sci. U.S.A. 1999
1664410 The GABAA receptor beta 3 subunit gene: characterization of a human cDNA from chromosome 15q11q13 and mapping to a region of conserved synteny on mouse chromosome 7

Wagstaff, J, Lalande, M, Chaillet, JR

Genomics 1991
15024690 Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations

Kwon, J, Nurnberger JI, Jr, Reich, T, O'Connor, SJ, Begleiter, H, Jones, K, Li, TK, Tian, H, Edenberg, HJ, Rice, J, Xuei, X, Crowe, RR, Bauer, LO, Goate, A, Dick, DM, Porjesz, B, Foroud, T, Almasy, L, Schuckit, MA, Hesselbrock, V

Am J Hum Genet 2004
1321750 Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit

Kemp, JA, Hadingham, K, Wingrove, P, Ragan, CI, Wafford, K, Whiting, P

Biochem Soc Trans 1992
2465923 Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits

Kettenmann, H, Pritchett, DB, Schofield, PR, Seeburg, PH, Sontheimer, H

FEBS Lett 1989
Catalyst Activity

chloride channel activity of GABR heteropentamers:GABA [plasma membrane]

Orthologous Events
Cross References
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