The actions of synaptically released zinc at hippocampal mossy fiber synapses.
Zn2+ is present at high concentrations in the synaptic vesicles of hippocampal mossy fibers. We have used Zn2+ chelators and the mocha mutant mouse to address the physiological role of Zn2+ in this pathway. Zn2+ is not involved in the unique presynaptic plasticities observed at mossy fiber synapses but is coreleased with glutamate from these synapses, both spontaneously and with electrical stimulation, where it exerts a strong modulatory effect on the NMDA receptors. Zn2+ tonically occupies the high-affinity binding site of NMDA receptors at mossy fiber synapses, whereas the lower affinity voltage-dependent Zn2+ binding site is occupied during action potential driven-release. We conclude that Zn2+ is a modulatory neurotransmitter released from mossy fiber synapses and plays an important role in shaping the NMDA receptor response at these synapses.
Vogt
K
K
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA.
Mellor
J
J
Tong
G
G
Nicoll
R
R
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D051379:Mice; D008817:Mice, Mutant Strains; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000502:physiology*
D002614:Chelating Agents; D016194:Receptors, N-Methyl-D-Aspartate; D004492:Edetic Acid; D015032:Zinc