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Trafficking and potential assembly patterns of ε‐containing GABA A receptors
Author(s) -
Jones Brian L.,
Henderson Leslie P.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04833.x
Subject(s) - cys loop receptors , receptor , protein subunit , gabaa receptor , gabaa rho receptor , recombinant dna , g alpha subunit , biophysics , biology , gamma subunit , microbiology and biotechnology , beta (programming language) , biochemistry , alpha (finance) , chemistry , acetylcholine receptor , medicine , gene , construct validity , nursing , nicotinic acetylcholine receptor , computer science , patient satisfaction , programming language
Incorporation of the ε subunit into the GABA A receptor has been suggested to confer unusual, but variable, biophysical and pharmacological characteristics to both recombinant and native receptors. Due to their structural similarity with the γ subunits, ε subunits have been assumed to substitute at the single position of the γ subunit in assembled receptors. However, prior work suggests that functional variability in ε‐containing receptors may reflect alternative sites of incorporation and of not just one, but possibly multiple ε subunits in the pentameric receptor complex. Here we present data indicating that increased expression of ε, in conjunction with α 2 and β 3 subunits, results in expression of GABA A receptors with correspondingly altered rectification, deactivation and levels of spontaneous openings, but not increased total current density. We also provide data that the ε subunit, like the β 3 subunit, can self‐export and data from chimeric receptors suggesting that similarities between the assembly domains of the β 3 and the ε subunits may allow the ε subunit to replace the β, as well as the γ, subunit. The substitution of an ε for a β, as well as the γ subunit and formation of receptors with alternative patterns of assembly with respect to ε incorporation may underlie the observed variability in both biophysical and pharmacological properties noted not only in recombinant, but also in native receptors.