loreclezole and zinc-chloride

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.

Topics: Allosteric Regulation; Animals; Anticonvulsants; Carbolines; Chlorides; Convulsants; Dentate Gyrus; Diazepam; Dose-Response Relationship, Drug; Female; gamma-Aminobutyric Acid; Hypnotics and Sedatives; In Vitro Techniques; Male; Membrane Potentials; Neurons; Patch-Clamp Techniques; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Triazoles; Zinc Compounds; Zolpidem