GABAA receptor function and regional analysis of subunit mRNAs in long-sleep and short-sleep mouse brain

Nancy R. Zahniser, Kari J. Buck, Pamela Curella, Susan J. McQuilkin, Donna Wilson-Shaw, Christine L. Miller, Ronald L. Klein, Kim A. Heidenreich, Wendy J. Keir, James M. Sikela, R. Adron Harris

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The greater sensitivity of long-sleep (LS), as compared with short-sleep (SS), mice to ethanol is due in part to differences in GABAA receptor function in specific brain regions. To determine if differences in subunit composition of GABAA receptors contribute to this differential sensitivity, we measured α1 and γ2 subunit mRNAs with Northern analysis and in situ hybridization and γ2S, γ2L and α6 subunit mRNAs with polymerase chain reaction (PCR) amplification. No differences in mRNAs in whole brain were apparent by Northern analysis. In situ hybridization revealed that α1 and γ2 subunit mRNAs were co-localized in many brain regions but that they still had distinct patterns of hybridization. However, the few differences observed between LS and SS mice in the levels of hybridization for these subunits did not show a regional distribution consistent with ethanol sensitivity differences. Similar ratios of γ2L and γ2S subunit mRNAs were found in LS and SS mouse cerebral cortex and hippocampus, and both mouse lines expressed essentially only γ2L subunit mRNA in cerebellum, mRNA for the α6 subunit was detected only in cerebellum and also was qualitatively similar between LS and SS mice. Studies of muscimol-stimulated 36Cl- uptake by cortical membrane vesicles confirmed earlier findings that ethanol does not enhance function of GABAA receptors in SS mice when assayed at 30°C. However, at 34°C ethanol did increase this function in SS mice although the enhancement remained greater in LS mice. These functional results, together with the results showing similar levels of α1, γ2S, γ2L and α6 subunits in LS and SS mice, suggest that the ethanol-insensitivity of SS mouse GABAA receptors cannot be due solely to lack of subunits required for ethanol action and further suggest that differences in catalytic mechanisms affecting post-translational processing may account for some genetic differences in ethanol sensitivity of GABAA receptors.

Original languageEnglish (US)
Pages (from-to)196-206
Number of pages11
JournalMolecular Brain Research
Issue number3
StatePublished - Jul 1992
Externally publishedYes


  • Chloride flux
  • Ethanol
  • GABA receptor
  • In situ hybridization
  • Long-sleep mouse
  • Polymerase chain reaction
  • Short-sleep mouse
  • mRNA
  • α Subunit
  • α Subunit
  • γ Subunit
  • γ Subunit
  • γ Subunit

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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