Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression

J Neurosci. 1997 Feb 15;17(4):1350-62. doi: 10.1523/JNEUROSCI.17-04-01350.1997.


Cerebellar granule cells express six GABAA receptor subunits abundantly (alpha1, alpha6, beta2, beta3, gamma2, and delta) and assemble various pentameric receptor subtypes with unknown subunit compositions; however, the rules guiding receptor subunit assembly are unclear. Here, removal of intact alpha6 protein from cerebellar granule cells allowed perturbations in other subunit levels to be studied. Exon 8 of the mouse alpha6 subunit gene was disrupted by homologous recombination. In alpha6 -/- granule cells, the delta subunit was selectively degraded as seen by immunoprecipitation, immunocytochemistry, and immunoblot analysis with delta subunit-specific antibodies. The delta subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a post-translational loss of the delta subunit. These results provide genetic evidence for a specific association between the alpha6 and delta subunits. Because in alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot rescue the delta subunit, certain potential subunit combinations may not be found in wild-type cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Benzodiazepines / pharmacology
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • GABA Agonists / metabolism
  • GABA Antagonists / metabolism
  • GABA-A Receptor Antagonists*
  • Gene Expression Regulation*
  • Ion Channel Gating*
  • Ion Channels / metabolism*
  • Lac Operon
  • Ligands
  • Male
  • Mice
  • Mice, Knockout / genetics
  • Muscimol / metabolism
  • Neurons / metabolism
  • Protein Processing, Post-Translational
  • Pyridazines / metabolism
  • RNA, Messenger / metabolism
  • Receptors, GABA-A / genetics*
  • Receptors, GABA-A / metabolism


  • GABA Agonists
  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • Ion Channels
  • Ligands
  • Pyridazines
  • RNA, Messenger
  • Receptors, GABA-A
  • Benzodiazepines
  • Muscimol
  • gabazine

Associated data

  • GENBANK/AJ222970