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

Content Provider	Semantic Scholar
Author	Ruiz, Arnaud J. Walker, Matthew C. Fabian-Fine, Ruth Kullmann, Dimitri Michael
Copyright Year	2004
Abstract	Depending on their subunit composition, GABA(A) receptors can be highly sensitive to Zn(2+). Although a pathological role for Zn(2+)-mediated inhibition of GABA(A) receptors has been postulated, no direct evidence exists that endogenous Zn(2+) can modulate GABAergic signaling in the brain. A possible explanation is that Zn(2+) 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 Zn(2+). Here, we show, using combined Timm's method and post-embedding immunogold, that the same mossy fiber varicosities can contain both GABA and Zn(2+). Chelating Zn(2+) 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 Zn(2+). 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 Zn(2+) and are consistent with GABA release at Zn(2+)-containing mossy fiber synapses.
Starting Page	047201
Ending Page	047201
Page Count	1
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://jn.physiology.org/content/early/2003/10/15/jn.00755.2003.full.pdf
Alternate Webpage(s)	http://jn.physiology.org/content/91/2/1091.full.pdf
Alternate Webpage(s)	http://jn.physiology.org/content/jn/91/2/1091.full.pdf
PubMed reference number	14561688v1
Volume Number	91
Issue Number	2
Journal	Journal of neurophysiology
Language	English
Access Restriction	Open
Subject Keyword	CA3 field Calcium Depressive disorder Edetic Acid Embedding Inhibitory Postsynaptic Currents Interneurons Iron Chelating Agents Mossy Fibers, Hippocampal Postsynaptic Current Pyramidal Cells Structure of dentate gyrus Subgroup Synapses Tissue fiber gamma-Aminobutyric Acid micacocidin A mossy fiber
Content Type	Text
Resource Type	Article