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The Journal of Neuroscience, July 30, 2003, 23(17):6847-6855
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Evidence for Chelatable Zinc in the Extracellular Space of the Hippocampus, But Little Evidence for Synaptic Release of Zn
Alan R. Kay
Biological Sciences, University of Iowa, Iowa City, Iowa 52242
Zinc colocalizes with glutamate in the synaptic vesicles of certain
glutamatergic vesicles in the mammalian brain. Here, I introduce a method for
detecting Zn in the extracellular space of brain slices and another method for
detecting the passage of Zn out of the slice. In both cases, the fluorimetric
Zn probe FluoZin-3 is used in conjunction with a slow Zn chelator, Ca-EDTA, to
reduce background fluorescence. In addition, a new Zn chelator,
ethylenediiminodi-2-pentanedioic acid, with little affinity for Ca or Mg is
introduced. These tools are then used to show that little Zn ( 2
nM) is released during the course of synaptic transmission into the
extracellular space. However, when hippocampal slices are subjected to a high
potassium stimulus (50 mM) combined with an increase in osmolarity, Zn is
externalized in the Timm's-stained areas (6 nM). This stimulus
also leads to even greater Zn elevations in area CA1 that is only weakly
stained by the Timm's method. Nevertheless, even under these conditions,
little if any Zn makes its way out of the slices. I present evidence for a
layer of Zn in the extracellular space that maps onto the Timm's stained
region of the hippocampus. This Zn veneer appears to be loosely associated
with molecules in the extracellular space and may be the raison d'être
for vesicular Zn.
Key words: zinc; fluorimetric; hippocampus; chelator; glutamate; fluorescence
Received Mar. 10, 2003;
revised May. 28, 2003;
accepted Jun. 5, 2003.
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