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Hippocampal neurons express GABA A receptor insensitive to diazepam in hyperexcitable conditions
1Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA. jk8t@virginia.edu
Purpose:
To define the properties of gamma-aminobutyric acid-type A (GABAA) receptors expressed on dentate granule cells in neonatal rats and to define the impact of prolonged seizures on GABAA receptors in 28- to 35-day-old rats.
Methods:
Whole GABAA receptor currents were recorded from acutely isolated dentate granule cells. Cells were isolated from 7- to 14-day-old rats for the first experiment. For the second experiment, cells were isolated from 28- to 35-day-old naive rats and rats that had undergone 45 minutes of status epilepticus. Modulation of GABAA receptor currents by diazepam (DZP), zinc, and zolpidem was studied.
Results:
In 7- to 14-day-old rats, dentate granule cells express DZP- and zolpidem-insensitive, zinc-sensitive GABAA receptors. In 28- to 35-day-old rats, dentate granule cells express DZP-sensitive GABAA receptors. At the latter age, prolonged seizures render GABAA receptors DZP-insensitive.
Conclusion:
Hippocampal dentate granule cells express DZP-insensitive receptors in hyperexcitable states. These receptors are likely to contain alpha4 subunit.