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

We examined if the drug sensitivity of GABA, receptors in dentate gyrus gra nule neurons changed during the whole-cell current time-course. Effects of drugs on currents evoked immediately (the peak current) upon drug applicati on and currents remaining about two seconds later (semi-plateau current) we re compared. The apparent affinity for GABA (EC,,) of the peak and the semi -plateau current were 14 and 4 muM, respectively. Bicuculline inhibited 50% of the peak and the semi-plateau current (IC50) at 7 and 36 muM, respectiv ely, while 100 muM was required for full inhibition of the 100 muM GABA-evo ked current. Zinc inhibited about 50% of the peak current with an IC,, valu e of 94 muM whereas biphasic, but complete inhibition of the semi-plateau c urrent was recorded with IC,, values of 3 and 558 muM. The decay phase of t he 100 muM GABA-evoked current was fitted by a fast (tau (1), 100-300 ms) a nd a slow (tau (2), 1-2 s) time-constants in all cells. The relative curren t amplitude associated with the fast (A1) and the slow (A2) component varie d. The Al current amplitude appeared more sensitive to bicuculline than the A2 current while the opposite was true for zinc. The results are consisten t with heterogenous population of functional GABA, receptors in the dentate gyrus granule neurons. (C) 2001 Elsevier Science Ltd. All rights reserved.