Journal article
Concentrations of extracellular free zinc (pZn) e in the central nervous system during simple anesthetization, ischemia and reperfusion
Experimental neurology, Vol.198(2), pp.285-293
2006
DOI: 10.1016/j.expneurol.2005.08.030
PMID: 16443223
Abstract
“Free Zn2+” (rapidly exchangeable Zn2+) is stored along with glutamate in the presynaptic terminals of specific specialized (gluzinergic) cerebrocortical neurons. This synaptically releasable Zn2+ has been recognized as a potent modulator of glutamatergic transmission and as a key toxin in excitotoxic neuronal injury. Surprisingly (despite abundant work on bound zinc), neither the baseline concentration of free Zn2+ in the brain nor the presumed co-release of free Zn2+ and glutamate has ever been directly observed in the intact brain in vivo. Here, we show for the first time in dialysates of rat and rabbit brain and human CSF samples from lumbar punctures that: (i) the resting or “tonic” level of free Zn2+ signal in the extracellular fluid of the rat, rabbit and human being is approximately 19 nM (95% range: 5–25 nM). This concentration is 15,000-fold lower than the “300 μM” concentration which is often used as the “physiological” concentration of free zinc for stimulating neural tissue. (ii) During ischemia and reperfusion in the rabbit, free zinc and glutamate are (as has often been presumed) released together into the extracellular fluid. (iii) Unexpectedly, Zn2+ is also released alone (without glutamate) at a variable concentration for several hours during the reperfusion aftermath following ischemia. The source(s) of this latter prolonged release of Zn2+ is/are presumed to be non-synaptic and is/are now under investigation. We conclude that both Zn2+ and glutamate signaling occur in excitotoxicity, perhaps by two (or more) different release mechanisms.
Details
- Title: Subtitle
- Concentrations of extracellular free zinc (pZn) e in the central nervous system during simple anesthetization, ischemia and reperfusion
- Creators
- C.J Frederickson - NeuroBioTex, Inc., 101 Christopher Columbus Blvd., Galveston, TX 77550, USAL.J Giblin - NeuroBioTex, Inc., 101 Christopher Columbus Blvd., Galveston, TX 77550, USAA Krężel - Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX 77550, USAD.J McAdoo - Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USAR.N Muelle - Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77550, USAY Zeng - NeuroBioTex, Inc., 101 Christopher Columbus Blvd., Galveston, TX 77550, USAR.V Balaji - NeuroBioTex, Inc., 101 Christopher Columbus Blvd., Galveston, TX 77550, USAR Masalha - NeuroBioTex, Inc., 101 Christopher Columbus Blvd., Galveston, TX 77550, USAR.B Thompson - Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USAC.A Fierke - Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USAJ.M Sarvey - Department of Pharmacology, Uniform Services University Health Sciences, Bethesda, MD 20814, USAM de Valdenebro - Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77550, USAD.S Prough - Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77550, USAM.H Zornow - Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77550, USA
- Resource Type
- Journal article
- Publication Details
- Experimental neurology, Vol.198(2), pp.285-293
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.expneurol.2005.08.030
- PMID
- 16443223
- ISSN
- 0014-4886
- eISSN
- 1090-2430
- Language
- English
- Date published
- 2006
- Academic Unit
- Anesthesia
- Record Identifier
- 9984007291002771
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