The GABA<sub>A</sub>-rho receptor (previously known as the GABA<sub>C</sub> receptor) is a subclass of GABA<sub>A</sub> receptors composed entirely of rho (ÃÂ) subunits. GABA<sub>A</sub> receptors including those of the ÃÂ-subclass are ligand-gated ion channels responsible for mediating the effects of gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the brain. The GABA<sub>A</sub>-ÃÂ receptor, like other GABA<sub>A</sub> receptors, is expressed in many areas of the brain, but in contrast to other GABA<sub>A</sub> receptors, the GABA<sub>A</sub>-ÃÂ receptor has especially high expression in the retina.
A second type of ionotropic GABA receptor, insensitive to typical allosteric modulators of GABA<sub>A</sub> receptor channels such as benzodiazepines and barbiturates, was designated GABA<sub>á</sub> receptor. Native responses of the GABA<sub>C</sub> receptor type occur in retinal bipolar or horizontal cells across vertebrate species.
GABA<sub>á</sub> receptors are exclusively composed of à(rho) subunits that are related to GABA<sub>A</sub> receptor subunits. Although the term "GABA<sub>á</sub> receptor" is frequently used, GABA<sub>á</sub> may be viewed as a variant within the GABA<sub>A</sub> receptor family. Others have argued that the differences between GABA<sub>á</sub> and GABA<sub>A</sub> receptors are large enough to justify maintaining the distinction between these two subclasses of GABA receptors. However, since GABA<sub>á</sub> receptors are closely related in sequence, structure, and function to GABA<sub>A</sub> receptors and since other GABA<sub>A</sub> receptors besides those containing àsubunits appear to exhibit GABA<sub>á</sub> pharmacology, the Nomenclature Committee of the IUPHAR has recommended that the GABA<sub>á</sub> term no longer be used and these àreceptors should be designated as the àsubfamily of the GABA<sub>A</sub> receptors (GABA<sub>A</sub>-ÃÂ).
In addition to containing a GABA binding site, the GABA<sub>A</sub>-ÃÂ receptor complex conducts chloride ions across neuronal membranes. Binding of GABA to the receptor results in opening of this channel. When the reversal potential of chloride is less than the membrane potential, chloride ions flow down their electrochemical gradient into the cell. This influx of chloride ions lowers the membrane potential of the neuron, thus hyperpolarizing it, making it more difficult for these cells to conduct electrical impulses in the form of an action potential. Following stimulation by GABA, the chloride current produced by GABA<sub>A</sub>-ÃÂ receptors is slow to initiate but sustained in duration. In contrast, the GABA<sub>A</sub> receptor current has a rapid onset and short duration. GABA is about 10 times more potent at GABA<sub>A</sub>-ÃÂ than it is at most GABA<sub>A</sub> receptors.
Like other ligand-gated ion channels, the GABA<sub>A</sub>-ÃÂ chloride channel is formed by oligomerization of five subunits arranged about a fivefold symmetry axis to form a central ion conducting pore. To date, three GABA<sub>A</sub>-ÃÂ receptor subunits have been identified in humans:
The above three subunits coassemble either to form functional homo-pentamers (ÃÂ1<sub>5</sub>, ÃÂ2<sub>5</sub>, ÃÂ3<sub>5</sub>) or hetero-pentamers (ÃÂ1<sub>m</sub>ÃÂ2<sub>n</sub>, ÃÂ2<sub>m</sub>ÃÂ3<sub>n</sub> where m + n = 5).
There is also evidence that ÃÂ1 subunits can form hetero-pentameric complexes with GABA<sub>A</sub> receptor ó2 subunits.
There are several pharmacological differences that distinguish GABA<sub>A</sub>-ÃÂ from GABA<sub>A</sub> and GABA<sub>B</sub> receptors. For example, GABA<sub>A</sub>-ÃÂ receptors are:
In humans, GABA<sub>A</sub>-ÃÂ receptor subunits ÃÂ1 and ÃÂ2 are encoded by the and genes which are found on chromosome 6 whereas the gene for ÃÂ3 is found on chromosome 3. Mutations in the ÃÂ1 or ÃÂ2 genes may be responsible for some cases of autosomal recessive retinitis pigmentosa.