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Developmental up-regulation and agonist-dependent down-regulation of GABAA receptor subunit mRNAs in chick cortical neurons

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We have used quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to analyze the expression of {GABAA} receptor subunit genes in cultured neurons from the chick embryo cerebral cortex. During maturation of the neurons between day 2 and day 8 in culture, levels of the α1 subunit transcript (per ng total RNA) increased 3.8 ± 0.3 fold, while those for the β2S and β4S subunits increased 2.4 ± 0.4 and 1.8 ± 0.2 fold, respectively. The accumulation of the β4S subunit mRNA was more rapid than those encoding either the α1 or β2S polypeptides. After 4 days in culture the β4S subunit transcript level reached 105 ± 7.7% of that found after 8 days, while the corresponding amounts for the α1 and β2S subunit mRNAs were 50 ± 7.1% and 44 ± 10.7%, respectively. On the other hand, no significant differences were observed in the level of either the γ1 or the γ2S subunit mRNA during development in vitro. Likewise, the ratios of the large/small splice variants (β2 = 0.16 ± 0.02; β4 = 0.57 ± 0.02; γ2 = 0.30 ± 0.06) did not show detectable changes during this period. To study the down-regulation of the mRNAs, a single dose of 100 μM {GABA} was added to the culture medium. After 7 days of exposure to GABA, the levels of transcripts for the α1, β2, β4, γ1, and γ2 subunits and their splice variants (where present) were all reduced by 47–65% compared to untreated controls. However, {GABA} treatment for 4 days did not produce a significant change in the level of the α1 subunit mRNA. The subunit specificity observed for developmental up-regulation and the lack of specificity in down-regulation suggests that mRNA down-regulation does not involve suppression of a developmental process. Comparisons with previous work indicate that the GABA-dependent reduction in the levels of subunit transcripts occurs after the loss of {GABAA} receptor binding sites [Hablitz et al., Brain Res., 501 (1989) 332–338] and subunit polypeptides [Calkin and Barnes, J. Biol. Chem., 269 (1994) 1548–1553]. Thus, for the down-regulation of {GABAA} receptors, it appears that translational or post-translational mechanisms may take precedence over the controlled synthesis or stability of subunit mRNAs.

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  • Date:

    31 October 1994

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  • Library of Congress:

    RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

  • Dewey Decimal Classification:

    571 Physiology & related subjects


Barnes Jr., E. M., Baumgartner, B. J., Harvey, R. J., & Darlison, M. G. (1994). Developmental up-regulation and agonist-dependent down-regulation of GABAA receptor subunit mRNAs in chick cortical neurons. Molecular Brain Research, 26(1-2), 9-17.


Molecular Biology; Cellular and Molecular Neuroscience

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