Synaptically released zinc: Physiological functions and pathological effects

  • Christopher J. Frederickson
  • Ashley I. Bush


In addition to its familiar role as a component of metalloproteins, zinc is also sequestered in the presynaptic vesicles of a specialized type of neurons called ‘zinc-containing’ neurons. Here we review the physiological and pathological effects of the release of zinc from these zinc-containing synaptic terminals. The best-established physiological role of synaptically released zinc is the tonic modulation of brain excitability through modulation of amino acid receptors; prominent pathological effects include acceleration of plaque deposition in Alzheimer’s disease and exacerbation of excitotoxic neuron injury. Synaptically released zinc functions as a conventional synaptic neurotransmitter or neuromodulator, being released into the cleft, then recycled into the presynaptic terminal. Beyond this, zinc also has the highly unconventional property that it passes into postsynaptic neurons during synaptic events, functioning analogously to calcium in this regard, as a transmembrane neural signal. To stimulate comparisons of zinc signals with calcium signals, we have compiled a list of the important parameters of calcium signals and zinc signals. More speculatively, we hypothesize that zinc signals may loosely mimic phosphate ‘signals’ in the sense that signal zinc ions may commonly bind to proteins in a lasting manner (i.e., ‘zincylating’ the proteins) with consequential changes in protein structure and function.


Mossy Fiber Dorsal Cochlear Nucleus Intracellular Zinc Presynaptic Vesicle Mossy Fiber Synapse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • Christopher J. Frederickson
    • 1
  • Ashley I. Bush
    • 2
  1. 1.NeuroBioTex, Inc., Biomedical Engineering and Anatomy and NeuroscienceThe University of Texas Medical BranchGalvestonUSA
  2. 2.Laboratory for Oxidation BiologyHarvard Medical SchoolBostonUSA

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