Trafficking and potential assembly patterns of epsilon-containing GABAA receptors

J Neurochem. 2007 Nov;103(3):1258-71. doi: 10.1111/j.1471-4159.2007.04833.x. Epub 2007 Aug 20.


Incorporation of the epsilon subunit into the GABAA 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 gamma subunits, epsilon subunits have been assumed to substitute at the single position of the gamma subunit in assembled receptors. However, prior work suggests that functional variability in epsilon-containing receptors may reflect alternative sites of incorporation and of not just one, but possibly multiple epsilon subunits in the pentameric receptor complex. Here we present data indicating that increased expression of epsilon, in conjunction with alpha2 and beta3 subunits, results in expression of GABAA receptors with correspondingly altered rectification, deactivation and levels of spontaneous openings, but not increased total current density. We also provide data that the epsilon subunit, like the beta3 subunit, can self-export and data from chimeric receptors suggesting that similarities between the assembly domains of the beta3 and the epsilon subunits may allow the epsilon subunit to replace the beta, as well as the gamma, subunit. The substitution of an epsilon for a beta, as well as the gamma subunit and formation of receptors with alternative patterns of assembly with respect to epsilon incorporation may underlie the observed variability in both biophysical and pharmacological properties noted not only in recombinant, but also in native receptors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Cell Membrane / metabolism*
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Macromolecular Substances / chemistry
  • Macromolecular Substances / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Models, Molecular
  • Neural Inhibition / genetics
  • Protein Structure, Tertiary / drug effects
  • Protein Structure, Tertiary / physiology
  • Protein Subunits / drug effects
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport / physiology
  • Receptors, GABA-A / biosynthesis*
  • Receptors, GABA-A / chemistry
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Synaptic Transmission / genetics
  • Transfection
  • Zinc / metabolism
  • Zinc / pharmacology
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology


  • GABRE protein, human
  • Macromolecular Substances
  • Protein Subunits
  • Receptors, GABA-A
  • Recombinant Proteins
  • gamma-Aminobutyric Acid
  • Zinc