Hippocampal neurons express GABA A receptor insensitive to diazepam in hyperexcitable conditions.
OBJECTIVE
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.


CONCLUSIONS
Hippocampal dentate granule cells express DZP-insensitive receptors in hyperexcitable states. These receptors are likely to contain alpha4 subunit.
Kapur
J
J
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA. jk8t@virginia.edu
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology*; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013226:Status Epilepticus / Q000209:etiology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D011963:Receptors, GABA-A; D003975:Diazepam