Functional heterogeneity of hippocampal GABAA receptors

gamma-Aminobutyric acid type A (GABAA) 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 microM GABA, respectively, with the Hill coefficient being greater than unity. The main-state conductance of GABAA 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-beta-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 GABAA receptor isoforms in neurons of the early postnatal hippocampus, which may subserve different inhibitory control mechanisms in this brain region.