Synaptically-released zinc inhibits N-methyl-D-aspartate receptor activation at recurrent mossy fiber synapses.
Hippocampal slices from pilocarpine-treated rats were used to explore the effect of zinc released at mossy fiber synapses on dentate granule cells. Chelation of zinc enhanced the N-methyl-D-aspartate (NMDA) receptor-mediated component of the excitatory postsynaptic current (EPSC), but did not affect the AMPA/kainate receptor-mediated component. Its effect was detectable only at negative membrane potentials and was pathway specific. Thus corelease of zinc reduces the ability of glutamate to activate postsynaptic NMDA receptors. Through this action, zinc would be expected to attenuate granule cell epileptiform activity supported by the recurrent mossy fiber pathway.
Molnár
P
P
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Nadler
J V
JV
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000378:metabolism*
D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018721:Muscarinic Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; D015032:Zinc