Zinc modulation of GABA A receptor-mediated chloride flux in rat hippocampal slices
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 whi...
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| Published in: | Brain research Vol. 691; no. 1; pp. 125 - 132 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier B.V
11-09-1995
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| Abstract | 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. |
|---|---|
| AbstractList | 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. |
| Author | Gordey, Marina Olsen, Richard W. Spigelman, Igor Kang, Maenghee |
| Author_xml | – sequence: 1 givenname: Marina surname: Gordey fullname: Gordey, Marina organization: Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles, CA, USA – sequence: 2 givenname: Maenghee surname: Kang fullname: Kang, Maenghee organization: Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles, CA, USA – sequence: 3 givenname: Richard W. surname: Olsen fullname: Olsen, Richard W. organization: Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles, CA, USA – sequence: 4 givenname: Igor surname: Spigelman fullname: Spigelman, Igor organization: Brain Research Institute, University of California, Los Angeles, CA, USA |
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| Keywords | Excitability Dentate gyrus TPEN CA1 pyramidal neuron Inhibition |
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| Snippet | 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... |
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| StartPage | 125 |
| SubjectTerms | CA1 pyramidal neuron Dentate gyrus Excitability Inhibition TPEN |
| Title | Zinc modulation of GABA A receptor-mediated chloride flux in rat hippocampal slices |
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