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Sci. Signal., 13 May 2008
Vol. 1, Issue 19, p. re3
[DOI: 10.1126/stke.119re3]


Is Zinc a Neuromodulator?

Alan R. Kay1* and Katalin Tóth2

1Department of Biology, 336 BB, University of Iowa, Iowa City, IA 52242, USA.
2Centre de Recherche and Department of Psychiatry, Université Laval Robert Giffard, 2601 chemin de la Canardière, F6550, Québec, QC G1J 2G3, Canada.

Gloss: This review, with 3 figures and 57 references, describes the evidence that the cation Zn2+ acts as a modulator of synaptic activity. Beginning with a discussion of the criteria that zinc would have to meet in order to be classified as a neuromodulator and the use of chelators for intercepting zinc in the synaptic cleft, the authors then consider different models for zinc’s action at synapses, ranging from free diffusion of zinc to bound zinc in the extracellular space and a possible action within synaptic vesicles. The article wraps up with suggested experimental approaches that may help resolve the questions surrounding the role of zinc in the central nervous system.

*Corresponding author. E-mail, alan-kay{at}

Citation: A. R. Kay, K. Tóth, Is Zinc a Neuromodulator? Sci. Signal. 1, re3 (2008).

Synaptic Zn2+ Inhibits Neurotransmitter Release by Promoting Endocannabinoid Synthesis.
T. Perez-Rosello, C. T. Anderson, F. J. Schopfer, Y. Zhao, D. Gilad, S. R. Salvatore, B. A. Freeman, M. Hershfinkel, E. Aizenman, and T. Tzounopoulos (2013)
J. Neurosci. 33, 9259-9272
   Abstract »    Full Text »    PDF »
Kv3 channel assembly, trafficking and activity are regulated by zinc through different binding sites.
Y. Gu, J. Barry, and C. Gu (2013)
J. Physiol. 591, 2491-2507
   Abstract »    Full Text »    PDF »
The Intronic GABRG2 Mutation, IVS6+2T->G, Associated with Childhood Absence Epilepsy Altered Subunit mRNA Intron Splicing, Activated Nonsense-Mediated Decay, and Produced a Stable Truncated {gamma}2 Subunit.
M. Tian and R. L. Macdonald (2012)
J. Neurosci. 32, 5937-5952
   Abstract »    Full Text »    PDF »
Vesicular Zinc Regulates the Ca2+ Sensitivity of a Subpopulation of Presynaptic Vesicles at Hippocampal Mossy Fiber Terminals.
N. Lavoie, D. V. Jeyaraju, M. R. Peralta III, L. Seress, L. Pellegrini, and K. Toth (2011)
J. Neurosci. 31, 18251-18265
   Abstract »    Full Text »    PDF »
Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones.
A. Evstratova and K. Toth (2011)
J. Physiol. 589, 5677-5689
   Abstract »    Full Text »    PDF »
The Neurophysiology and Pathology of Brain Zinc.
S. L. Sensi, P. Paoletti, J.-Y. Koh, E. Aizenman, A. I. Bush, and M. Hershfinkel (2011)
J. Neurosci. 31, 16076-16085
   Abstract »    Full Text »    PDF »

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