Heterogeneity of functional GABA A receptors in rat dentate gyrus neurons revealed by a change in response to drugs during the whole-cell current time-course

We examined if the drug sensitivity of GABAA receptors in dentate gyrus granule neurons changed during the whole-cell current time-course. Effects of drugs on currents evoked immediately (the peak current) upon drug application and currents remaining about two seconds later (semi-plateau current) were compared. The apparent affinity for GABA (EC50) of the peak and the semi-plateau current were 14 and 4 μM, respectively. Bicuculline inhibited 50% of the peak and the semi-plateau current (IC50) at 7 and 36 μM, respectively, while 100 μM was required for full inhibition of the 100 μM GABA-evoked current. Zinc inhibited about 50% of the peak current with an IC50 value of 94 μM whereas biphasic, but complete inhibition of the semi-plateau current was recorded with IC50 values of 3 and 558 μM. The decay phase of the 100 μM GABA-evoked current was fitted by a fast (τ1, 100-300 ms) and a slow (τ2, 1-2 s) time-constants in all cells. The relative current amplitude associated with the fast (A1) and the slow (A2) component varied. The A1 current amplitude appeared more sensitive to bicuculline than the A2 current while the opposite was true for zinc. The results are consistent with heterogenous population of functional GABAA receptors in the dentate gyrus granule neurons