Homomeric rho 1 GABA channels: activation properties and domains

Recept Channels. 1994;2(3):227-36.


Expression of human rho 1 subunits in Xenopus laevis oocytes forms homomeric GABA-activated chloride channels with activation and pharmacological properties distinct from those of typical heteromeric GABA channels (e.g., alpha 1 beta 2 gamma 2). Here, we describe these rho 1 activation features and use site-directed mutagenesis to identify amino acids involved in GABA-mediated activation. In comparison to heteromeric GABA channels (alpha 1 beta 2 gamma 2), GABA channels comprised of rho 1 subunits are approximately 40-fold more sensitive to GABA, activate 8.3-fold more slowly (at a GABA concentration equal to their respective EC50S), do not desensitize with maintained agonist application, and close approximately 8-fold more slowly after agonist removal. Site-directed mutagenesis of rho 1 GABA channels has identified five amino acids (Y198, Y200, Y241, T244, and Y247) located between the N-terminal extracellular cysteine loop and first membrane spanning domain, that when conservatively mutated, significantly impaired GABA-mediated activation. These five residues are grouped in two domains that correspond in position to the putative agonist-binding domains previously identified for the beta 2 subunit of alpha 1 beta 2 gamma 2 GABA channels. Y198, T244, and Y247 correspond directly to crucial amino acids identified in the beta 2 subunit; Y200 and Y241 do not. These differences may account, in part, for the unique activation and pharmacological features of homomeric rho 1 GABA channels.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chloride Channels / chemistry
  • Chloride Channels / drug effects
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Crotonates / pharmacology
  • Eye Proteins / chemistry
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Female
  • Humans
  • Membrane Potentials / drug effects
  • Microinjections
  • Molecular Sequence Data
  • Muscimol / pharmacology
  • Mutagenesis, Site-Directed
  • Oocytes
  • Protein Conformation
  • RNA, Complementary / administration & dosage
  • RNA, Complementary / genetics
  • Receptors, GABA-A / chemistry
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Retina / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Xenopus laevis
  • gamma-Aminobutyric Acid / pharmacology


  • Chloride Channels
  • Crotonates
  • Eye Proteins
  • RNA, Complementary
  • Receptors, GABA-A
  • Recombinant Fusion Proteins
  • 4-aminocrotonic acid
  • Muscimol
  • gamma-Aminobutyric Acid