GABAA receptor fundamentals (benzodiazepines)

[Kdem]

It sort of came up in a different thread, but I'm still not quite sure.

Per wiki: https://en.wikipedia.org/wiki/GABAA_receptor#Target_for_benzodiazepines

'While the majority of GABA_A receptors (those containing α₁-, α₂-, α₃-, or α₅-subunits) are benzodiazepine sensitive, there exists a minority of GABA_A receptors (α₄- or α₆-subunit containing) which are insensitive to classical 1,4-benzodiazepines' and 'GABA_A receptor is a pentameric transmembrane receptor that consists of five subunits arranged around a central pore.'

Originally I believed that most if not all GABAA receptors had al subunits (alpha1,2,3,5 anway).
But ... does each GABAA receptor have only one type of alpha subunit like alpha1 or alpha 2 etc ? I think I got it all wrong ...

 

[serotonin2A]

Alpha-1 is the most common alpha subunit. A single GABA-A receptor contains two alpha subunits, which can be homogeneous or heterogeneous.

https://www.ncbi.nlm.nih.gov/pubmed/10454469

 

[Kdem]

Thanks for that. But what are the somewhat common alpha ... combinations ?
I mean, is anything possibly ? Like alpha1, alpha3 on the same receptor ?

 

[serotonin2A]

The main thing controlling the composition is what subunit-coding genes are being expressed in individual neurons. So if a cell in the amygdala simultaneously transcribes the genes coding for the alpha-1, beta-2, and gamma-2 subunits, then that is how the new GABA-A receptors will be built. There are probably networks of transcription factors that coordinate the production of particular subunit combinations, and those systems will determine what range of structures are possible. In terms of theoretical possibilities, I think any two alpha-subunits could be combined together, but not all of the resulting receptor subtypes would necessarily be useful.

 

[Limpet_Chicken]

There is the GABAc/GABAa-rho receptor, isn't that now viewed as a subtype of GABAaR owing to its sensitivity to muscimol? that lacks the alpha-type subunits entirely, and is composed entirely of 3 rho-subtypes, although according to wikipedia might form heteromers with y2

 

[serotonin2A]

There is the GABAc/GABAa-rho receptor, isn't that now viewed as a subtype of GABAaR owing to its sensitivity to muscimol? that lacks the alpha-type subunits entirely, and is composed entirely of 3 rho-subtypes, although according to wikipedia might form heteromers with y2

The exact classification is still being worked out, but it is reasonable to classify it as a GABA-A subtype.

 

[Limpet_Chicken]

How so? because this type or types are insensitive to bicuculline, which, I believed was one of the defining characteristics of GABAaRs.

 

[serotonin2A]

^ Receptor nomenclature is no longer defined pharmacologically. Molecular biology is now used to guide classification whenever possible.