Differences between GABA Receptor Binding to Membranes from Cerebellum during Postnatal Development and from Cultured Cerebellar Granule Cells

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Abstract
GABA receptor binding sites were determined in membranes from cerebella of 7-, 15- and 60-day-old rats and cerebellar granule cells derived from 7-day-old rats and cultured for 8 days using [3H]GABA as the ligand and nonradioactive GABA to measure non-specific binding. Membranes from cerebellum at all postnatal stages exhibited at least two binding sites for GABA with binding constants around 7–9 and 150–750 nM, respectively. The total number of binding sites expressed on the basis of total protein increased 10 times between 7 and 60 days of age and 2 times between 15 and 60 days. The latter increase could be quantitatively accounted for by an increase in the number of low affinity sites. In contrast to this, membranes from cultured granule cells only exhibited the high affinity binding site (KD 7.1±0.5 nM) and the number of binding sites was comparable to that of cerebellar membranes from rats of the corresponding age (15 days old). GABA analogues such as muscimol, piperidine-4-sulphonic acid, homo-β-proline, THIP, and isoguvacine were potent displacers of GABA binding to cultured granule cells, whereas nipecotic acid and guvacine had no effect.