Functional Heterogeneity of Hippocampal GABAA Receptors

γ-Aminobutyric acid type A (GABA_A) receptors were studied in cultured neurons taken from rat hippocampus at early postnatal stages. GABA-induced whole-cell currents showed a broad range of peak amplitudes and time-courses of desensitization. Dose – response curves of rapidly and slowly desensitizing cells revealed EC₅₀ values of 8.5 and 37.3 μM GABA, respectively, with the Hill coefficient being greater than unity. The main-state conductance of GABA_A receptor channels was 28 – 31 pS in all cells. GABA responses of low-affinity cells were more strongly affected by benzodiazepine receptor agonists (e.g. flunitrazepam, clonazepam) and inverse agonists (e.g. methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate), as compared to cells exhibiting high-affinity GABA responses. Currents were also potentiated by zolpidem, but were little affected by Ro 15-4513 and Zn²⁺. These data suggest the presence of physiologically and pharmacologically distinct GABA_A receptor isoforms in neurons of the early postnatal hippocampus, which may subserve different inhibitory control mechanisms in this brain region.