Zinc modulation of GABA A receptor-mediated chloride flux in rat hippocampal slices

• Published in: Brain research Vol. 691; no. 1; pp. 125 - 132
• Main Authors: Gordey, Marina, Kang, Maenghee, Olsen, Richard W., Spigelman, Igor
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 11-09-1995
• Subjects: CA1 pyramidal neuron; Dentate gyrus; Excitability; Inhibition; TPEN; Excitability; Dentate gyrus; TPEN; CA1 pyramidal neuron; Inhibition
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00653-8

We studied the effect of ZnCl
2 application on GABA
A receptor-mediated
36Cl
− 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 μM)-evoked
36Cl
− flux was significantly reduced by ZnCl
2 (100 μM) in hippocampal microsacs. In hippocampal slices, muscimol (50 μM)-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 ZnCl
2, 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 μM), caused a significant increase in muscimol-evoked
36Cl
− efflux only in DG slices (57.2 ± 7.0%), suggesting that GABA
A receptors in the DG of rat hippocampus under physiological conditions may function under the inhibitory influence of endogenous chelatable zinc. In intracellular recordings, ZnCl
2 (100 μM) application had no effect on the responses to GABA applied perisomatically or in the dendritic region of CA1 neurons. The lack of Zn
2+ effect on the postsynaptic GABA
A 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.