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      Pharmacological properties of gamma-aminobutyric acidA receptors from acutely dissociated rat dentate granule cells.

      Molecular pharmacology
      Allosteric Regulation, Animals, Anticonvulsants, pharmacology, Carbolines, Chlorides, Convulsants, Dentate Gyrus, cytology, physiology, Diazepam, Dose-Response Relationship, Drug, Female, Hypnotics and Sedatives, In Vitro Techniques, Male, Membrane Potentials, drug effects, Neurons, Patch-Clamp Techniques, Pyridines, Rats, Rats, Sprague-Dawley, Receptors, GABA-A, isolation & purification, Triazoles, Zinc Compounds, gamma-Aminobutyric Acid

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          Abstract

          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.

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