GABAC receptor

protein
Name = gamma-aminobutyric acid (GABA) receptor, rho 1
caption =


width =
HGNCid = 4090
Symbol = GABRR1
AltSymbols =
EntrezGene = 2569
OMIM = 137161
RefSeq = NM_002042
UniProt = P24046
PDB =
ECnumber =
Chromosome = 6
Arm = q
Band = 14
LocusSupplementaryData = -q21protein
Name = gamma-aminobutyric acid (GABA) receptor, rho 2
caption =


width =
HGNCid = 4091
Symbol = GABRR2
AltSymbols =
EntrezGene = 2570
OMIM = 137162
RefSeq = NM_002043
UniProt = P28476
PDB =
ECnumber =
Chromosome = 6
Arm = q
Band = 14
LocusSupplementaryData = -q21protein
Name = gamma-aminobutyric acid (GABA) receptor, rho 3
caption =


width =
HGNCid = 17969
Symbol = GABRR3
AltSymbols =
EntrezGene = 200959
OMIM =
RefSeq = NM_001105580
UniProt = Q9UIV9
PDB =
ECnumber =
Chromosome = 3
Arm = q
Band = 12.2
LocusSupplementaryData = The GABA_C receptor is one of two ligand-gated ion channels responsible for mediating the effects of Gamma-Amino Butyric Acid (GABA), the major inhibitory neurotransmitter in the brain. The GABA_C receptor, like the closely-related GABA_A receptor, is expressed in many areas of the brain, but in contrast to GABA_A, the GABA_C receptor has especially high expression in the retina. [Qian H. 2000. [http://webvision.med.utah.edu/GABA-C.htm GABAc receptors in the vertebrate retina] . Retrieved on February 14, 2007.]

Function

In addition to containing a GABA binding site, the GABA_C receptor complex conducts chloride ions across neuronal membranes. Binding of GABA to the receptor results in opening of this channel, allowing chloride ions to flow down their electrochemical gradient into the cell. This increase in chloride current stabilizes the resting potential, making it more difficult for these cells conduct electrical impulses. Following stimulation by GABA, the chloride current produced by GABA_C receptors is slow to initiate but sustained in duration. In contrast, the GABA_A receptor current has a rapid onset and short duration. GABA is about 10 times more potent at GABA_C than it is at most GABA_A receptors.Martin IL and Dunn SMJ. [http://www.tocris.com/pdfs/gabarev.pdf GABA receptors] A review of GABA and the receptors to which it binds. Tocris Cookson LTD.]

tructure

Like other ligand-gated ion channels, the GABA_C chloride channel is formed by oligomerization of five subunits arranged about a five-fold symmetry axis to form a central ion conducting pore. To date, three GABA_C receptor subunits have been identified in humans:
* ρ1 (Gene|GABRR1)
* ρ2 (Gene|GABRR2)
* ρ3 (Gene|GABRR3)

The above three subunits coassemble either to form functional homo-pentamers (ρ1₅, ρ2₅, ρ3₅) or hetero-pentamers (ρ1_mρ2_n, ρ2_mρ3_n where m + n = 5).cite journal |author=Enz R, Cutting GR|title=Molecular composition of GABAC receptors|journal= Vision Res |volume= 38 |issue= 10 |pages= 1431–41 |year= 1998 |pmid= 9667009 | doi = 10.1016/S0042-6989(97)00277-0] cite journal |author=Ogurusu T, Yanagi K, Watanabe M, Fukaya M, Shingai R|title=Localization of GABA receptor rho 2 and rho 3 subunits in rat brain and functional expression of homo-oligomeric rho 3 receptors and hetero-oligomeric rho 2 rho 3 receptors|journal= Receptors Channels |volume= 6 |issue= 6 |pages= 463–75 |year= 1999 |pmid= 10635063 ]

There is also evidence that ρ1 subunits can form hetero-pentameric complexes with γ2 subunits of GABA_A receptorcite journal |author=Qian H, Ripps H|title=Response kinetics and pharmacological properties of heteromeric receptors formed by coassembly of GABA ρ- and γ2-subunits|journal= Proc R Soc Lond B|volume= 266 |pages= 2419–25 |year= 1999 |pmid= 10643085 | doi = 10.1098/rspb.1999.0941] .

Pharmacology

There are several pharmacological differences that distinguish GABA_C from GABA_A and GABA_B receptors.cite journal |author=Chebib M, Johnston GA|title=GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology|journal= J Med Chem |volume= 43 |issue= 8 |pages= 1427–47 |year= 2000|doi=10.1021/jm9904349 |pmid= 10780899 ] For example, GABA_C receptors are:

* selectively activated by (+)-CAMP [(+)-cis-2-aminomethylcyclopropane-carboxylic acid] and blocked by TPMPA [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid] ;
* not sensitive to the GABA_B agonist baclofen nor the GABA_A receptor antagonist bicuculline;
* not modulated by many GABA_A receptor modulators such as barbiturates, benzodiazepines, and neuroactive steroids.

Genetics

In humans, GABA_C receptor subunits ρ1 and ρ2 are encoded by the Gene|GABRR1 and Gene|GABRR2 genes which are found on chromosome 6 whereas the Gene|GABRR3 gene for ρ3 is found on chromosome 3. Mutations in the ρ1 or ρ2 genes may be responsible for some cases of autosomal recessive retinitis pigmentosa.cite journal |author=Marcos I, Ruiz A, Blaschak CJ, Borrego S, Cutting GR, Antinolo G|title=Mutation analysis of GABRR1 and GABRR2 in autosomal recessive retinitis pigmentosa|journal= J Med Genet |volume= 37 |issue= 6 |pages= E5 |year= 1998 |pmid= 10851258 | doi = 10.1136/jmg.37.6.e5]

References

ee also

*GABA_A receptor
*GABA_B receptor
*Gamma-aminobutyric acid