Structural and functional characterization of the gamma 1 subunit of GABAA/benzodiazepine receptors

EMBO J. 1990 Oct;9(10):3261-7. doi: 10.1002/j.1460-2075.1990.tb07525.x.


The GABAA receptor gamma 1 subunit of human, rat and bovine origin was molecularly cloned and compared with the gamma 2 subunit in structure and function. Both gamma subunit variants share 74% sequence similarity and are prominently synthesized in often distinct areas of the central nervous system as documented by in situ hybridization. When co-expressed with alpha and beta subunits in Xenopus oocytes and mammalian cells, the gamma variants mediate the potentiation of GABA evoked currents by benzodiazepines and help generate high-affinity binding sites for these drugs. However, these sites show disparate pharmacological properties which, for receptors assembled from alpha 1, beta 1 and gamma 1 subunits, are characterized by the conspicuous loss in affinity for neutral antagonists (e.g. flumazenil) and negative modulators (e.g. DMCM). These findings reveal a pronounced effect of gamma subunit variants on GABAA/benzodiazepine receptor pharmacology.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / metabolism*
  • Cattle
  • Cloning, Molecular
  • DNA / genetics
  • DNA / isolation & purification
  • Gene Library
  • Genetic Variation
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Oligonucleotide Probes
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Rats
  • Receptors, GABA-A / genetics*
  • Receptors, GABA-A / metabolism
  • Recombinant Proteins / metabolism
  • Sequence Homology, Nucleic Acid


  • Macromolecular Substances
  • Oligonucleotide Probes
  • RNA, Messenger
  • Receptors, GABA-A
  • Recombinant Proteins
  • DNA