Subunit assembly rules for GABAa receptors

The GABAA receptor subunit combinations found in brain are partly governed by which cell types express which genes (e.g., Wisden et al., 1992) and partly by preferential partnering of subunits within a given cell (e.g., Jones et al., 1997); for example, the a4 and a6 subunits assemble preferentially with the 8 subunit (Jones et al., 1997; Peng et al., 2002). The majority of mammalian brain GABAA receptors are probably apg2 combinations. The subunit ratio is probably 2a/2p/1g (Ernst et al., 2003). Some receptors also contain different a and p sub-units, e.g., a1a2p2g2 (Benke et al., 2004). According to Benke et al., 2004, who analysed whole mouse brain samples, the a1a1pg2 combination is the most abundant GABAA receptor subtype in the brain (61% of total). Other combinations were found in smaller quantities: a1a2pg2 (13%), a1a3pg2 (15%), a2a2pg2 (12%), a2a3pg2(2%) and a3a3pg2 (4%). Within the a1-containing receptor population, most receptors are a1a1pg2, whereas in the a2- and a3-containing receptor populations, receptors with two different a subunit types predominate (Benke et al., 2004). Of course, these percentages are from homogenized brain; within particular cell types, some of these rare subtypes will be the most important receptor subtype. Other receptor subtypes relevant for the basal ganglia are predicted from subunit expression patterns as a4p8 (or possibly a4p Bencsits et al., 1999) in the striatum and a1p2g1 in the globus pallidus.

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