GABA receptor subunits

Cutting, GR, Lu, L, O Hara, BF, Kasch, LM, Montrose-Rafizadeh, C, Donovan, DM, Shimada, S, Antonarakis, SE, Guggino, WB, Uhl, GR et al. (1991) Cloning of the y-aminobutyric acid (GABA) rho 1 cDNA a GABA receptor subunit highly expressed in the retina. Proc. Natl. Acad. Sci. USA 88 2673-2677. 

Recently, Low et al. (11) found that a specific, GABA receptor subunit may mediate the therapeutic effects of the BZDs. Thus, in mice, a knock-in point mutation for the aj versus ag subunit rendered diazepam ineffective for its anxiolytic effects. This indicates that the efficacy of BZDs is mediated by a 2 GABA receptors. 

Collins AL, Ma D, Whitehead PL, Martin ER, Wright HH, Abramson RK, Hussman JP, Haines JL, Cuccaro ML, Gilbert JR, Pericak-Vance MA (2006) Investigation of autism and GABA receptor subunit genes in multiple ethnic groups. Neurogenetics 7 167-174. 

TABLE 3. Distribution of GABA receptor subunit mRNAs in rat cerebellum... 

Laurie DJ, Seeburg PH, Wisden W (1992) The distribution of 13 GABA, receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum. J. Neurosci, 12, 1063-1076. 

Persohn E, Malherbe P, Richards JG (1992) Comparative molecular neuroanatomy of cloned GABA receptor subunits in the rat CNS. J. Comp. Neurol., 326, 193-216. 

Pritchett DB, Sontheimer H, Shivers BD, Ymer S, Kettenmann H, Schofield PR, Seeburg PH (1989) Importance of a novel GABA receptor subunit for benzodiazepine pharmacology. Nature, 338, 582-585. 

Nineteen different ionotropic GABA receptor subunits, named ai 6, P 3, 7i 3, S, e, 71 and d and 3, have been cloned from vertebrates. Experiments using recombinant expression and immunoprecipitation indicate that native vertebrate GABAa receptors contain at least a, fi and y subunits, sometimes also with <5, s, K ox 0 subunits, while GABAc receptors are believed to be composed only of p subunits. 

LCCH3 has 47% identity to vertebrate GABA receptor / subunits, but is unlikely to be a subunit of native insect GABA receptors. Although it can form functional heteromultimers with Rdl subunits, these are unlike any known native insect GABA receptors in that they are bicucculine-sensitive, PTX-insensitive and undergo a slow desensitization [26, 49). Furthermore, the distributions of LCCH3 and Rdl in the Drosophila nervous system do not overlap [50]. 

Figure 9 compares the amino acid sequences of the second transmembrane a-helix region of GABA receptor subunits. The alanine-to-serine mutation of the pore-lining amino acid of the housefly RDL subunit accounts for the... 

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