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 GABA(A) 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 (EC(50)) of the peak and the semi-plateau current were 14 and 4 microM, respectively. Bicuculline inhibited 50% of the peak and the semi-plateau current (IC(50)) at 7 and 36 microM, respectively, while 100 microM was required for full inhibition of the 100 microM GABA-evoked current. Zinc inhibited about 50% of the peak current with an IC(50) value of 94 microM whereas biphasic, but complete inhibition of the semi-plateau current was recorded with IC(50) values of 3 and 558 microM. The decay phase of the 100 microM GABA-evoked current was fitted by a fast (tau(1), 100-300 ms) and a slow (tau(2), 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 GABA(A) receptors in the dentate gyrus granule neurons.
Lim
M S
MS
Membrane Biology Program, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia.
Birnir
B
B
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D007700:Kinetics; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D015032:Zinc; D001640:Bicuculline