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Endogenous zinc inhibits GABA(A) receptors in a hippocampal pathway

Ruiz, A; Walker, MC; Fabian-Fine, R; Kullmann, DM; (2004) Endogenous zinc inhibits GABA(A) receptors in a hippocampal pathway. J NEUROPHYSIOL , 91 (2) 1091 - 1096. 10.1152/jn.00755.2003.

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Abstract

Depending on their subunit composition, GABA(A) receptors can be highly sensitive to Zn2+. Although a pathological role for Zn2+-mediated inhibition of GABA(A) receptors has been postulated, no direct evidence exists that endogenous Zn2+ can modulate GABAergic signaling in the brain. A possible explanation is that Zn2+ is mainly localized to a subset of glutamatergic synapses. Hippocampal mossy fibers are unusual in that they are glutamatergic but have also been reported to contain GABA and Zn2+. Here, we show, using combined Timm's method and post-embedding immunogold, that the same mossy fiber varicosities can contain both GABA and Zn2+. Chelating Zn2+ with either calcium-saturated EDTA or N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine had no effect on stratum-radiatum-evoked inhibitory postsynaptic currents (IPSCs), but enhanced IPSCs evoked by stimuli designed to recruit dentate granule cells. We also show that IPSCs recorded in CA3 pyramidal neurons in acute hippocampal slices are depressed by exogenous Zn2+. This depression was of similar amplitude whether the IPSCs were evoked by stimulation in s. radiatum ( to recruit local interneurons) or in the s. granulosum of the dentate gyrus ( to recruit mossy fibers). These results show for the first time that GABAergic IPSCs can be modulated by endogenous Zn2+ and are consistent with GABA release at Zn2+-containing mossy fiber synapses.

Type: Article
Title: Endogenous zinc inhibits GABA(A) receptors in a hippocampal pathway
DOI: 10.1152/jn.00755.2003
Keywords: MOSSY FIBER SYNAPSES, SYNAPTICALLY-RELEASED ZINC, TEMPORAL-LOBE EPILEPSY, RAT HIPPOCAMPUS, GRANULE CELLS, GLUTAMATE-DECARBOXYLASE, CALCIUM CHANNELS, DENTATE GYRUS, MODULATION, TERMINALS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/134421
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