Chronic GABA treatment downregulates the GABAA receptor α2 and α3 subunit mRNAS as well as polypeptide expression in primary cultured cerebral cortical neurons

Molina C. Mhatre, Maharaj K. Ticku

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Chronic GABA exposure of mammalian primary cultured cortical neurons results in a downregulation of the GABA-benzodiazepine receptor complex. In the present study, the mRNA levels, as well as polypeptide expression, for the GABAA receptor α2 and α3 subunits in cultured embryonic mouse cerebral cortical neurons (7 day old) were examined using northern analysis and immunoblotting techniques following chronic GABA treatment. The α1 subunit mRNA or polypeptide could not be detected in these neurons. The steady state levels of mRNA for the GABAA receptor α2 and α3 subunits showed a decrease in comparison with untreated neurons. There was no change in the level of the β actin or poly(A)+ RNA under the same experimental conditions. This agonist-induced reduction in the GABAA receptor α2 and α3 subunit mRNA was blocked by the concomitant exposure of neurons to R 5135, an antagonist of GABAA receptor. The polypeptide expression for the GABAA receptor α2 and α3 subunits in chronically GABA-treated neurons also showed a decline and this change was also blocked by the concomitant exposure of cells to GABA and R 5135. These results indicate that the chronic exposure of the GABAA receptor complex to agonist downregulates the expression of the α subunits of the receptor complex, which may be related to an observed decreases in the number of binding sites and GABA-induced 36Cl-influx in the cortical neurons.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalMolecular Brain Research
Volume24
Issue number1-4
DOIs
StatePublished - Jul 1994

Keywords

  • Cortical neuron
  • Downregulation
  • GABA receptor
  • α-Subunit mRNA
  • α-Subunit polypeptide

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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