Rapid translocation of zn2+ from presynaptic terminals into postsynaptic
hippocampal neurons following physiological stimulation.
Li1, Yang, Christopher J. Hough2, Sang Won Suh3, John M. Sarvey1 & Christopher
J. Frederickson3.
Departments of 1Pharmacology and 2Psychiatry, Uniformed Services University of
the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814, USA. 3Center
for Biomedical Engineering and Department of Anatomy and Neuroscience, University
of Texas Medical Branch, Galveston, TX 77555, USA
APStracts 8:0229J, 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). 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.
Received 29 December 2000; accepted in final form 25 May 2001
APS Manuscript Number J928-0.
Article publication pending Am J Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 31 July 2001