Bidirectional Regulation of GABAA Receptor α1 and α6 Subunit Expression by a Cyclic AMP‐Mediated Signalling Mechanism in Cerebellar Granule Cells in Primary Culture

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Abstract
Forskolin treatment of cerebellar granule cells in culture resulted in bidirectional regulation of the expression of GABAA receptor alpha1 and alpha6 subunits. Thus, forskolin applied at 2 days in vitro (DIV) increased expression of the alpha1 subunit but decreased the expression of the alpha6 subunit. Values with respect to control cultures, both assayed at 9 DIV by immunoblotting, were 310 +/- 48% for alpha1 and 25 +/- 16% for the alpha6 subunit. Similar effects were evoked following chronic treatment with both dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine. Dideoxyforskolin had no effect on the level of expression of either the alpha1 or the alpha6 GABAA receptor subunits. The changes in subunit expression were accompanied by a 1.7-fold increase in number of total specific [3H]Ro 15-4513 binding sites expressed by intact cerebellar granule cells. This increase in total binding sites was accommodated by a 2.7-fold increase in number of diazepam-sensitive Ro 15-4513 binding sites in accordance with the observed increase in alpha1 subunit expression. The number of diazepam-insensitive subtype of binding sites were not significantly changed. These results suggest that GABAA receptor subtype expression can be differentially regulated by intracellular cyclic AMP concentration.

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