GABAC receptor

The GABAC 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 GABAC receptor, like the closely-related GABAA receptor, is expressed in many areas of the brain, but in contrast to GABAA, the GABAC receptor has especially high expression in the retina.

In addition to containing a GABA binding site, the GABAC 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 GABAC receptors is slow to initiate but sustained in duration. In contrast, the GABAA receptor current has a rapid onset and short duration. GABA is about 10 times more potent at GABAC than it is at most GABAA receptors.

Structure
Like other ligand-gated ion channels, the GABAC 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 GABAC receptor subunits have been identified in humans:
 * ρ1
 * ρ2
 * ρ3

The above three subunits coassemble either to form functional homo-pentamers (ρ15, ρ25, ρ35) or hetero-pentamers (ρ1mρ2n, ρ2mρ3n where m + n = 5).

Pharmacology
There are several pharmacological differences that distinquish GABAC from GABAA and GABAB receptors. For example, GABAC 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 GABAB agonist baclofen nor the GABAA receptor antagonist bicuculline;
 * not modulated by many GABAA receptor modulators such as barbiturates, benzodiazepines, and neuroactive steroids.

Genetics
In humans, GABAC receptor subunits ρ1 and ρ2 are encoded by the and  genes which are found on chromosome 6 whereas the  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.