Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J Neurophysiol 86 (5): 2597-2604

Copyright © 2001 by the American Physiological Society.

The Journal of Neurophysiology Vol. 86 No. 5 November 2001, pp. 2597-2604
Copyright ©2001 by the American Physiological Society

Rapid Translocation of Zn2+ From Presynaptic Terminals Into Postsynaptic Hippocampal Neurons After Physiological Stimulation

Yang Li,1 Christopher J. Hough,2 Sang Won Suh,3 John M. Sarvey,1 and Christopher J. Frederickson3,4

 1Department of Pharmacology and  2Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814;  3Center for Biomedical Engineering and Department of Anatomy and Neuroscience, University of Texas Medical Branch; and  4NeuroBioTex, Inc., Galveston, Texas 77555

Li, Yang, Christopher J. Hough, Sang Won Suh, John M. Sarvey, and Christopher J. Frederickson. Rapid Translocation of Zn2+ From Presynaptic Terminals Into Postsynaptic Hippocampal Neurons After Physiological Stimulation. J. Neurophysiol. 86: 2597-2604, 2001. Zn2+ is found in glutamatergic nerve terminals throughout the mammalian forebrain and has diverse extracellular and intracellular actions. The anatomical location and possible synaptic signaling role for this cation have led to the hypothesis that Zn2+ is released from presynaptic boutons, traverses the synaptic cleft, and enters postsynaptic neurons. However, these events have not been directly observed or characterized. Here we show, using microfluorescence imaging in rat hippocampal slices, that brief trains of electrical stimulation of mossy fibers caused immediate release of Zn2+ from synaptic terminals into the extracellular microenvironment. Release was induced across a broad range of stimulus intensities and frequencies, including those likely to induce long-term potentiation. The amount of Zn2+ release was dependent on stimulation frequency (1-200 Hz) and intensity. Release of Zn2+ required sodium-dependent action potentials and was dependent on extracellular Ca2+. Once released, Zn2+ crosses the synaptic cleft and enters postsynaptic neurons, producing increases in intracellular Zn2+ concentration. These results indicate that, like a neurotransmitter, Zn2+ is stored in synaptic vesicles and is released into the synaptic cleft. However, unlike conventional transmitters, it also enters postsynaptic neurons, where it may have manifold physiological functions as an intracellular second messenger.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A specific role for hippocampal mossy fiber's zinc in rapid storage of emotional memories.
J. Ceccom, H. Halley, S. Daumas, and J. M. Lassalle (2014)
Learn. Mem. 21, 287-297
   Abstract »    Full Text »    PDF »
Differential needs of zinc in the CA3 area of dorsal hippocampus for the consolidation of contextual fear and spatial memories.
J. Ceccom, E. Bouhsira, H. Halley, S. Daumas, and J. M. Lassalle (2013)
Learn. Mem. 20, 348-351
   Abstract »    Full Text »    PDF »
Synaptic Released Zinc Promotes Tau Hyperphosphorylation by Inhibition of Protein Phosphatase 2A (PP2A).
X.-Y. Sun, Y.-P. Wei, Y. Xiong, X.-C. Wang, A.-J. Xie, X.-L. Wang, Y. Yang, Q. Wang, Y.-M. Lu, R. Liu, et al. (2012)
J. Biol. Chem. 287, 11174-11182
   Abstract »    Full Text »    PDF »
Transient Receptor Potential Melastatin 1 (TRPM1) Is an Ion-conducting Plasma Membrane Channel Inhibited by Zinc Ions.
S. Lambert, A. Drews, O. Rizun, T. F. J. Wagner, A. Lis, S. Mannebach, S. Plant, M. Portz, M. Meissner, S. E. Philipp, et al. (2011)
J. Biol. Chem. 286, 12221-12233
   Abstract »    Full Text »    PDF »
Zinc-induced Neurotoxicity Mediated by Transient Receptor Potential Melastatin 7 Channels.
K. Inoue, D. Branigan, and Z.-G. Xiong (2010)
J. Biol. Chem. 285, 7430-7439
   Abstract »    Full Text »    PDF »
An Extracellular Cu2+ Binding Site in the Voltage Sensor of BK and Shaker Potassium Channels.
Z. Ma, K. Y. Wong, and F. T. Horrigan (2008)
J. Gen. Physiol. 131, 483-502
   Abstract »    Full Text »    PDF »
pH-Dependent Inhibition of Kainate Receptors by Zinc.
D. D. Mott, M. Benveniste, and R. J. Dingledine (2008)
J. Neurosci. 28, 1659-1671
   Abstract »    Full Text »    PDF »
Identification of Key Residues Coordinating Functional Inhibition of P2X7 Receptors by Zinc and Copper.
X. Liu, A. Surprenant, H.-J. Mao, S. Roger, R. Xia, H. Bradley, and L.-H. Jiang (2008)
Mol. Pharmacol. 73, 252-259
   Abstract »    Full Text »    PDF »
Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons.
H. X. Zhang and L. L. Thio (2007)
J Neurophysiol 98, 3666-3676
   Abstract »    Full Text »    PDF »
Zinc is a novel intracellular second messenger.
S. Yamasaki, K. Sakata-Sogawa, A. Hasegawa, T. Suzuki, K. Kabu, E. Sato, T. Kurosaki, S. Yamashita, M. Tokunaga, K. Nishida, et al. (2007)
J. Cell Biol. 177, 637-645
   Abstract »    Full Text »    PDF »
Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities.
J. P Bressler, L. Olivi, J. H. Cheong, Y. Kim, A. Maerten, and D. Bannon (2007)
Human and Experimental Toxicology 26, 221-229
   Abstract »    PDF »
Episodic ataxia type 1 mutation F184C alters Zn2+-induced modulation of the human K+ channel Kv1.4-Kv1.1/Kvbeta1.1.
P. Imbrici, M. C. D'Adamo, A. Cusimano, and M. Pessia (2007)
Am J Physiol Cell Physiol 292, C778-C787
   Abstract »    Full Text »    PDF »
Extracellular chelation of zinc does not affect hippocampal excitability and seizure-induced cell death in rats.
N. Lavoie, M. R. Peralta III, M. Chiasson, K. Lafortune, L. Pellegrini, L. Seress, and K. Toth (2007)
J. Physiol. 578, 275-289
   Abstract »    Full Text »    PDF »
Intracellular Zinc Elevation Measured with a "Calcium-Specific" Indicator during Ischemia and Reperfusion in Rat Hippocampus: A Question on Calcium Overload.
C. J. Stork and Y. V. Li (2006)
J. Neurosci. 26, 10430-10437
   Abstract »    Full Text »    PDF »
Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain..
L. Bonanni, M. Chachar, T. Jover-Mengual, H. Li, A. Jones, H. Yokota, D. Ofengeim, R. J. Flannery, T. Miyawaki, C.-H. Cho, et al. (2006)
J. Neurosci. 26, 6851-6862
   Abstract »    Full Text »    PDF »
Exocytosis of vesicular zinc reveals persistent depression of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3-CA1 synapse..
J. Qian and J. L. Noebels (2006)
J. Neurosci. 26, 6089-6095
   Abstract »    Full Text »    PDF »
Zinc and Mercuric Ions Distinguish TRESK from the Other Two-Pore-Domain K+ Channels.
G. Czirjak and P. Enyedi (2006)
Mol. Pharmacol. 69, 1024-1032
   Abstract »    Full Text »    PDF »
An Architectural Framework That May Lie at the Core of the Postsynaptic Density.
M. K. Baron, T. M. Boeckers, B. Vaida, S. Faham, M. Gingery, M. R. Sawaya, D. Salyer, E. D. Gundelfinger, and J. U. Bowie (2006)
Science 311, 531-535
   Abstract »    Full Text »    PDF »
Determinants of Zinc Potentiation on the {alpha}4 Subunit of Neuronal Nicotinic Receptors.
B. Hsiao, K. B. Mihalak, S. E. Repicky, D. Everhart, A. H. Mederos, A. Malhotra, and C. W. Luetje (2006)
Mol. Pharmacol. 69, 27-36
   Abstract »    Full Text »    PDF »
Blockade of calcium-permeable AMPA receptors protects hippocampal neurons against global ischemia-induced death.
K.-M. Noh, H. Yokota, T. Mashiko, P. E. Castillo, R. S. Zukin, and M. V. L. Bennett (2005)
PNAS 102, 12230-12235
   Abstract »    Full Text »    PDF »
Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse.
J. Qian and J. L Noebels (2005)
J. Physiol. 566, 747-758
   Abstract »    Full Text »    PDF »
Zinc inhibition of {gamma}-aminobutyric acid transporter 4 (GAT4) reveals a link between excitatory and inhibitory neurotransmission.
E. Cohen-Kfir, W. Lee, S. Eskandari, and N. Nelson (2005)
PNAS 102, 6154-6159
   Abstract »    Full Text »    PDF »
Two SUR1-specific Histidine Residues Mandatory for Zinc-induced Activation of the Rat KATP Channel.
V. Bancila, T. Cens, D. Monnier, F. Chanson, C. Faure, Y. Dunant, and A. Bloc (2005)
J. Biol. Chem. 280, 8793-8799
   Abstract »    Full Text »    PDF »
The Micromolar Zinc-Binding Domain on the NMDA Receptor Subunit NR2B.
J. Rachline, F. Perin-Dureau, A. Le Goff, J. Neyton, and P. Paoletti (2005)
J. Neurosci. 25, 308-317
   Abstract »    Full Text »    PDF »
Zinc Potentiates an Uncoupled Anion Conductance Associated with the Dopamine Transporter.
A.-K. Meinild, H. H. Sitte, and U. Gether (2004)
J. Biol. Chem. 279, 49671-49679
   Abstract »    Full Text »    PDF »
Late Calcium EDTA Rescues Hippocampal CA1 Neurons from Global Ischemia-Induced Death.
A. Calderone, T. Jover, T. Mashiko, K.-m. Noh, H. Tanaka, M. V. L. Bennett, and R. S. Zukin (2004)
J. Neurosci. 24, 9903-9913
   Abstract »    Full Text »    PDF »
Region Specific Micromodularity in the Uppermost Layers in Primate Cerebral Cortex.
N. Ichinohe and K. S. Rockland (2004)
Cereb Cortex 14, 1173-1184
   Abstract »    Full Text »    PDF »
Zn2+ Ions: Modulators of Excitatory and Inhibitory Synaptic Activity.
T. G. Smart, A. M. Hosie, and P. S. Miller (2004)
Neuroscientist 10, 432-442
   Abstract »    PDF »
Zinc is both an intracellular and extracellular regulator of KATP channel function.
A.-L. Prost, A. Bloc, N. Hussy, R. Derand, and M. Vivaudou (2004)
J. Physiol. 559, 157-167
   Abstract »    Full Text »    PDF »
Zinc and Excitotoxic Brain Injury: A New Model.
C. J. Frederickson, W. Maret, and M. P. Cuajungco (2004)
Neuroscientist 10, 18-25
   Abstract »    PDF »
Boutons Containing Vesicular Zinc Define a Subpopulation of Synapses with Low AMPAR Content in Rat Hippocampus.
C. B. Sindreu, H. Varoqui, J. D. Erickson, and J. Perez-Clausell (2003)
Cereb Cortex 13, 823-829
   Abstract »    Full Text »    PDF »
Evidence for Chelatable Zinc in the Extracellular Space of the Hippocampus, But Little Evidence for Synaptic Release of Zn.
A. R. Kay (2003)
J. Neurosci. 23, 6847-6855
   Abstract »    Full Text »    PDF »
Imaging Zinc: Old and New Tools.
C. Frederickson (2003)
Sci. STKE 2003, pe18
   Abstract »    Full Text »    PDF »
Do We Need Zinc to Think?.
Y. V. Li, C. J. Hough, and J. M. Sarvey (2003)
Sci. STKE 2003, pe19
   Abstract »    Full Text »    PDF »
Meeting of the minds: Metalloneurochemistry.
S. C. Burdette and S. J. Lippard (2003)
PNAS 100, 3605-3610
   Abstract »    Full Text »    PDF »
Suppression by Zinc of AMPA Receptor-Mediated Synaptic Transmission in the Retina.
D.-Q. Zhang, C. Ribelayga, S. C. Mangel, and D. G. McMahon (2002)
J Neurophysiol 88, 1245-1251
   Abstract »    Full Text »    PDF »
Mossy fiber Zn2+ spillover modulates heterosynaptic N-methyl-D-aspartate receptor activity in hippocampal CA3 circuits.
S. Ueno, M. Tsukamoto, T. Hirano, K. Kikuchi, M. K. Yamada, N. Nishiyama, T. Nagano, N. Matsuki, and Y. Ikegaya (2002)
J. Cell Biol. 158, 215-220
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882