FUNCTIONAL-HETEROGENEITY OF HIPPOCAMPAL GABA(A) RECEPTORS

Gamma-Aminobutyric acid type A (GABA(A)) receptors were studied in cul tured neurons taken from rat hippocampus at early postnatal stages. GA BA-induced whole-cell currents showed a broad range of peak amplitudes and time-courses of desensitization. Dose - response curves of rapidl y and slowly desensitizing cells revealed EC50 values of 8.5 and 37.3 muM GABA, respectively, with the Hill coefficient being greater than u nity. The main-state conductance of GABA(A) receptor channels was 28-3 1 pS in all cells. GABA responses of low-affinity cells were more stro ngly affected by benzodiazepine receptor agonists (e.g. flunitrazepam, clonazepam) and inverse agonists (e.g. 7-dimethoxy-4-ethyl-beta-carbo line-3-carboxylate), as compared to cells exhibiting high-affinity GAB A responses. Currents were also potentiated by zolpidem, but were litt le affected by Ro 15-4513 and Zn2+. These data suggest the presence of physiologically and pharmacologically distinct GABA(A) receptor isofo rms in neurons of the early postnatal hippocampus, which may subserve different inhibitory control mechanisms in this brain region.