Postnatal development of hippocampal dentate granule cell gamma-aminobutyric acidA receptor pharmacological...

Postnatal development of hippocampal dentate granule cell gamma-aminobutyric acidA (GABAA) receptor pharmacological properties was studied. Granule cells were acutely isolated from hippocampi of 7- to 14- and 45- to 52-day-old rats, and whole cell patch-clamp recordings were obtained. The sensitivity of GABAA receptors to GABA and modulation of GABAA receptor currents by benzodiazepines (BZ), zinc, furosemide, and loreclezole was studied. Multiple changes in the pharmacological properties of dentate granule-cell GABAA receptors occurred during the first 52 days of postnatal development: GABA-evoked maximal current increased with postnatal age; GABAA receptors changed from BZ type 3 in young rats to BZ type 1 in adult rats; furosemide and zinc inhibited GABAA receptor currents in young rats but not in adult rats; the fraction of cells that expressed loreclezole-sensitive GABAA receptors increased with postnatal age. These findings suggest that dentate granule cells in young and adult animals express pharmacologically distinct GABAA receptors and that the postnatal development of these receptors is prolonged, lasting at least 45 days. Comparison with the previously reported pharmacological properties of GABAA receptors on dentate granule cells acutely isolated from hippocampi of 28- to 35-day-old rats suggests that receptors expressed at that age have properties intermediate between young and adult rats.