Pharmacological properties of gamma-aminobutyric acidA receptors from acutely dissociated rat dentate granule cells.
The pharmacological properties of gamma-aminobutyric acid (GABA) type A receptor (GABAR) currents recorded from hippocampal dentate granule cells acutely dissociated from 28-35-day-old rats were characterized using the whole-cell patch-clamp technique. Granule cells were voltage-clamped to 0 mV, and GABA was applied using a modified U-tube rapid-application technique. All granule cells were moderately sensitive to GABA (EC50 = 47 microM). All granule cell GABAR currents were uniformly sensitive to Zn2+ (IC50 = 29 microM), diazepam (EC50 = 158 nM), zolpidem (EC50 = 75 nM), and dimethoxyl-4-ethyl-beta-carboline-3-carboxylate (IC50 = 60 nM). GABAR currents from only 50% of granule cells were sensitive to loreclezole (EC50 = 9 microM). These data suggest that hippocampal dentate granule cells expressed GABARs with distinctive pharmacological properties of two types: loreclezole-sensitive and -insensitive receptors. It is likely that these distinctive properties were due to the specific GABAR subtypes that assembled to produce distinct granule cell GABAR isoforms.
Kapur
J
J
Department of Neurology, University of Michigan Medical Center, Ann Arbor 48104-1687, USA. jkapur@umich.edu
Macdonald
R L
RL
D000494:Allosteric Regulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000927:Anticonvulsants; D002243:Carbolines; D002712:Chlorides; D003292:Convulsants; D006993:Hypnotics and Sedatives; D011725:Pyridines; D011963:Receptors, GABA-A; D014230:Triazoles; D017967:Zinc Compounds; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005680:gamma-Aminobutyric Acid; C066440:loreclezole; D000077334:Zolpidem; C016837:zinc chloride; D003975:Diazepam