GABAc receptor

GABAc receptors are defined by their insensitivity to bicuculline and their activation by conformationally restricted analogues of GABA such as CACA and (+)-CAMP (15, 2i -2-(aminomethyl)cyclopropanecarboxylic acid). They are blocked by picrotoxin but can be selectively antagonised by TPMPA (l,2,5,6-tetrahydropyridin4-ylphosphinic acid). Unlike GABAa receptors, they are not affected by benzodiazepines, barbiturates or anaesthetics (Barnard et al. 1998 Bormann 2000 Chebib and Johnston 2000). 

Figure 11.9 GAB Ac receptor pharmacology and structure, (a) Various GAB Ac agonists and antagonists described in the text. Picrotoxinin is the active component of picrotoxin and also acts at GABAa receptors, (b) Presumed subunit structures of GABAc receptors. The receptors can form as homomeric assemblies of p subunits but native receptors may be heteromeric assemblies of p subunits (e.g. pi and p2) or may contain both p and y subunits...

Johnston, GA (1996) GABAc receptors relatively simple transmitter-gated ion channels Trends... 

Wotring, VE, Chang, Y and Weiss, DS (1999) Permeability and single channel conductance of human homomeric rhol GABAc receptors. J. Physiol. (Land.) 521 Part 2, 327-336. 

Note Mammalian orthologs for the avian a8 and y4 subunits have not yet been identified. The p 1-3 subunit constitutes the GABAC receptors. 

The diversity of the GABAa subunits (Figure 3.2d) is reflected in a very complex pharmacology. Expression of the subunits in heterologous systems shows that the combinations a, (3, and y can yield functional receptors, indicating that the limitation in subunit combination is defined by expression levels and most likely cell-dependent assembly mechanisms also. The pj to p3 subunits mainly co-assemble with each other to form the GABAC receptors. 

Chang Y, Weiss DS. 1999. Channel opening locks agonist onto the GABAc receptor. Nat Neurosci 2 (3) 219. 

In the retina, homomeric receptors consisting of the p-subunit represent a particular class of GABA-gated chloride channels. Their GABA site is insensitive to bicuculline and baclofen and they are not modulated by barbiturates or benzodiazepines. Due to these distinctive features, the receptors are sometimes termed GABAc receptors (Bormann 2000), although they are be considered a homomeric class of GABAa receptors (Barnard et al. 1998). 

Kirischuk S, Akyeli J, Iosub R, Grantyn R (2003) Pre- and postsynaptic contribution of GABAC receptors to GABAergic synaptic transmission in rat collicular slices and cultures. Eur J Neurosci 18 752-8... 

Enz R, Cutting GR. 1998. Molecular composition of GABAC receptors. Vision Res 38 1431-1441. 

Qian HH, Pan Y, Zhu YJ, Khalili P (2005) Picrotoxin Accelerates Relaxation of GABAc Receptors. Mol Pharmacol 67 470... 

Lummis SC, Bean D, Harrison NJ, Lester HA, Dougherty DA. A cation-pi binding interaction with a tyrosine in the binding site of the gabac receptor. Chem. Biol. 2005 12 993-997. 

Lukasiewicz PD, Eggers ED, Sagdullaev BT, McCall MA (2004) GABAC receptor-mediated inliibidon in the redna. Vision Res 44 3289-3296. 

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