Localization and functional expression of alternatively spliced forms of the GABAA receptor γ2 subunit

James M. Sikela, Nancy J. Leidenheimer, Carla Gambarana, Kari J. Buck, Lie Huey Lin, Akbar S. Khan, Donna Wilson-Shaw, Ruth E. Siegel

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Recent studies have identified two alternatively spliced forms of the GABAA receptor γ2 subunit that differ by the presence (γ2L) or absence (γ2S) of an eight-amino acid segment. This insert in the γ2L isoform exists in the proposed cytoplasmic loop region, between M3 and M4, and contains a consensus sequence for phosphorylation by protein kinase C. To examine the regional distribution of this novel receptor subunit in the brain, γ2L subunit mRNA was detected using both in situ hybridization histochemistry and and PCR amplification methods. Hybridization histochemistry with a γ2L, subunit-specific oligonucleotide probe revealed that the γ2L, subunit mRNA is widely distributed throughout the mouse brain. The highest levels of expression are found in the cerebral cortex, hippocampus, olfactory lobe, and cerebellum. The presence of the γ2L, subunit in these regions was confirmed using PCR. Additionally, PCR experiments detected yes subunit mRNA in the cerebral cortex and hippocampus but not in the cerebellum. To examine the functional properties of the γ2 subunit isoforms, γ2S and γ2L, subunit mRNAs were coexpressed with α1β1 subunit mRNAs in Xenopus oocytes. These experiments indicate that the γ2L and γ2S subunit variants exhibit similar pharmacological properties, including the ability of both isoforms to confer diazepam sensitivity to the receptor complex. In addition, potentiation of GABA responses by pentobarbital in oocytes expressing either subunit isoform is similar. These data indicate that the presence or absence of the additional eight amino acids in the γ2 subunit isoforms does not appear to alter the response of the GABAA receptor complex to either benzodiazepines and barbiturates at the level of protein phosphorylation present in the oocyte.

Original languageEnglish (US)
Pages (from-to)338-343
Number of pages6
JournalMolecular and Cellular Neuroscience
Volume2
Issue number4
DOIs
StatePublished - Aug 1991

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Sikela, J. M., Leidenheimer, N. J., Gambarana, C., Buck, K. J., Lin, L. H., Khan, A. S., Wilson-Shaw, D., & Siegel, R. E. (1991). Localization and functional expression of alternatively spliced forms of the GABAA receptor γ2 subunit. Molecular and Cellular Neuroscience, 2(4), 338-343. https://doi.org/10.1016/1044-7431(91)90064-U