Zinc modulation of GABAA receptor-mediated chloride flux in rat hippocampal slices.
We studied the effect of ZnCl2 application on GABAA receptor-mediated 36CI- flux in microsacs prepared from whole rat hippocampus and in region-specific hippocampal slices. Slices were obtained from the dentate gyrus (DG), which contains the zinc-enriched hilar region, and from the CA1 region which contains lower levels of endogenous zinc. Muscimol (10 microM)-evoked 36Cl- flux was significantly reduced by ZnCl2 (100 microM) in hippocampal microsacs. In hippocampal slices, muscimol (50 microM)-evoked 36Cl- efflux was higher in CA1 (112.5 +/- 27.9% above basal efflux rate) than in DG slices (29.7 +/- 5.6%). In the presence of ZnCl2, the muscimol effect on efflux rate in CA1 and DG regions was decreased to 10.6 +/- 5.4% and 6.9 +/- 4.9%, respectively. Preincubation with the zinc chelator, tetrakis(2-pyridylmethyl)ethylenediamine (TPEN, 20 microM), caused a significant increase in muscimol-evoked 36Cl- efflux only in DG slices (57.2 +/- 7.0%), suggesting that GABAA receptors in the DG of rat hippocampus under physiological conditions may function under the inhibitory influence of endogenous chelatable zinc. In intracellular recordings, ZnCl2 (100 microM) application had no effect on the responses to GABA applied perisomatically or in the dendritic region of CA1 neurons. The lack of Zn2+ effect on the postsynaptic GABAA receptor-mediated responses suggests that the decreases of the 36Cl- efflux observed in the biochemical assays may be due to zinc action on neurons other than the principal pyramidal CA1 cells, and possibly the non-neuronal cell populations.
Gordey
M
M
Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles, USA.
Kang
M
M
Olsen
R W
RW
Spigelman
I
I
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005029:Ethylenediamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000037:antagonists & inhibitors; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D017967:Zinc Compounds / Q000494:pharmacology*
D002614:Chelating Agents; D002712:Chlorides; D005029:Ethylenediamines; D011963:Receptors, GABA-A; D017967:Zinc Compounds; D009118:Muscimol; C016837:zinc chloride; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine