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Zinc Biochemistry, Physiology, and Homeostasis pp 167–180Cite as

Synaptically released zinc: Physiological functions and pathological effects

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Abstract

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.

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References

  • Adlard PA, West AK, Vickers JC. 1998 Increased density of metallothionein I/II immunopositive cortical glial cells in the early stages of Alzheimer’s disease. Neurobiol Dis 5, 349–356.

    Article  PubMed  CAS  Google Scholar 

  • Atwood CS, Moir RD, Huang X, Scarpa RC, Bacarra NME, Romano DM, Hartshorn MA, Tanzi RE, Bush AI. 1998 Dramatic aggregation of Alzheimer Aß by Cu(II) is induced by conditions representing physiological acidosis. J Biol Chem 273, 12817–12826.

    Article  PubMed  CAS  Google Scholar 

  • Auld DS. 1995 Removal and replacement of metal ions in metal-lopeptidases. Methods Enzymol 248, 228–242.

    Article  PubMed  CAS  Google Scholar 

  • Backstrom JR, Miller CA, Tokes ZA. 1992 Characterization of neutral proteinases from Alzheimer-affected and control brain specimens, identification of calcium-dependent metalloproteinases from the hippocampus. J Neurochem 58, 983–992.

    Google Scholar 

  • Baranano DE, Ferris CD, Snyder SH. 2001 Atypical neural messengers. Trends Neurosci 24, 99–106.

    Article  PubMed  CAS  Google Scholar 

  • Beaulieu C, Dyck R, Cynader M. 1992 Enrichment of glutamate in zinc-containing terminals of the cat visual cortex. Neuroreport 10, 861–864.

    Article  Google Scholar 

  • Berg JM. 1990 Zinc finger domains: hypotheses and current knowledge. Annu Rev Biophys Biophys Chem 19, 405–421.

    Article  PubMed  CAS  Google Scholar 

  • Birinyi A, Parker D, Antal M, Shupliakov O. 2001 Zinc co-localizes with GABA and glycine in synapses in the lamprey spinal cord. J Comp Neurol 433, 208–221.

    Article  PubMed  CAS  Google Scholar 

  • Brown EM, MacLeod RJ. 2001 Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81, 239–297.

    PubMed  CAS  Google Scholar 

  • Bush AI, Pettingel WH, Multhaup G, Paradis MD, Vonsattel JP, Gusella JF, Beyreuther K, Masters CL, Tanzi RE. 1994a Rapid induction of Alzheimer A amyloid formation by zinc. Science 265, 1464–1467.

    Article  PubMed  CAS  Google Scholar 

  • Bush AI, Pettingel WH, Paradis MD, Tanzi RE. 1994b. Modulation of Aß adhesiveness and a secretase site cleavage by zinc. J Biol Chem 269, 12152–12158.

    PubMed  CAS  Google Scholar 

  • Bush AI, Huang X, Fairlie DP. 1999 The possible origin of free radicals from amyloid ß peptides in Alzheimer’s disease. Neurobiol Aging 20, 335–337.

    Article  Google Scholar 

  • Canzoniero LMT, Turetsky DM, Choi DW. 1999 Measurement of Intracellular Free Zinc Concentrations Accompanying Zinc-Induced Neuronal Death. J Neurosci 19 (RC31), 1–6.

    Google Scholar 

  • Casanovas-Aguilar C, Reblet C, Perez-Clausell J, Bueno-Lopez JL. 1998 Zinc-rich afferents to the rat neocortex, projections to the visual cortex traced with intracerebral selenite injections. J Chem Neuroanat 15, 97–109.

    Article  PubMed  CAS  Google Scholar 

  • Chen N, Moshaver A, Raymond LA. 1997 Differential sensitivity of recombinant N-methyl-D-aspartate receptor subtypes to zinc inhibition. Mol Pharmacol 51, 1015–1023.

    PubMed  CAS  Google Scholar 

  • Cherny RA, Atwood CS, Xilinas X, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim Y-S, Huang X, Goldstein LE, Moir RD, Lim JT, Zheng H, Beyreuther K, Tanzi RE, Masters CL, Bush AI. 2001 Treatment with a copper-zinc chelator markedly and rapidly inhibits ß-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 30, 665–676.

    Article  PubMed  CAS  Google Scholar 

  • Choi DW, Koh JY. 1998 Zinc and brain injury. Annu Rev Neurosci 21, 347–375.

    Article  PubMed  CAS  Google Scholar 

  • Christensen MK, Frederickson CJ. 1998 Zinc containing afferent projections to the rat corticomedial amygdaloid complex, a retrograde tracing study. J Comp Neurol 400, 375–390.

    Article  PubMed  CAS  Google Scholar 

  • Cole TB, Wenzel HJ, Kafer KE, Schwartzkroin PA, Palmiter RD. 1999 Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci USA 96, 1716–1721.

    Article  PubMed  CAS  Google Scholar 

  • Cole TB, Martyanova A, Palmiter RD. 2001 Removing zinc from synaptic vesicles does not impair spatial learning, memory, or sensorimotor functions in the mouse. Brain Res 891, 253–265.

    Article  PubMed  CAS  Google Scholar 

  • Cole TB, Robbins CA, Wenzel HJ, Schwartzkroin PA, Palmiter RD. 2000 Seizures and neuronal damage in mice lacking vesicular zinc. Epilepsy Res 39, 153–169.

    Article  PubMed  CAS  Google Scholar 

  • Coulter DA. 2000 Mossy fiber zinc and temporal lobe epilepsy, pathological association with altered `epileptic’ gammaaminobutyric acid A receptors in dentate granule cells. Epilepsia 41 (Suppl 6), S96 - S99.

    Article  PubMed  Google Scholar 

  • Cuajungco MP, Lees GJ. 1998 Nitric oxide generators produce accumulation of chelatable zinc in hippocampal neuronal perikarya. Brain Res 799, 118–129.

    Article  PubMed  CAS  Google Scholar 

  • Cuajungco MP, Lees GJ, Kydd RR, Tanzi RE, Bush AI. 2000 Zinc and Alzheimer’s disease, an update. Nutl Neurosci 2, 191–208.

    Google Scholar 

  • Danscher G. 1996 The autometallographic zinc-sulfide method. A new approach in vivo creation of nanometer sized zinc sulfide crystal lattices in zinc-enriched synaptic and secretory vesicles. J Histochem 28, 363–372.

    Article  Google Scholar 

  • Du Y, Ni BF, Glinn M, Dodel RC, Bales KR, Zhang Z, Hyslop PA, Paul SM. 1997 a2-macroglobulin as a ß-amyloid peptide-binding plasma protein. J Neurochem 69, 299–305.

    Google Scholar 

  • Dyck RH, Cynader MS. 1993 An interdigitated columnar mosaic of cytochrome oxidase, zinc, and neurotransmitter-related molecules in cat and monkey visual cortex. Proc Natl Acad Sci USA 90, 9066–9069.

    Article  PubMed  CAS  Google Scholar 

  • Franco-Pons N, Casanovas-Aguilar C, Arroyo S, Rumia J, PerezClausell J, Danscher G. 2000 Zinc-rich synaptic boutons in human temporal cortex biopsies. Neuroscience 98, 429–435.

    Article  PubMed  CAS  Google Scholar 

  • Frederickson CJ. 1989 Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol 31, 145–238.

    Article  PubMed  CAS  Google Scholar 

  • Frederickson CJ, Cuajungco MP, Suh SW. 2001 Nitric oxide causes apparent release of zinc from presynaptic boutons. Neuroscience (in press).

    Google Scholar 

  • Frederickson CJ, Danscher G. 1990 Zinc-containing neurons in the hippocampus and related CNS structures. Prog Brain Res 83, 7184.

    Google Scholar 

  • Frederickson CJ, Danscher G, Cravens KJ, Slomianka L, Sylvan LB. 1991 Staining for zinc reveals columnar patches in the hippocampus of the newborn rat. Soc Neurosci Abs 17, 1131.

    Google Scholar 

  • Frederickson CJ, Hernandez MD, Goik SA, Morton JD, McGinty JF. 1988 Loss of zinc staining from hippocampal mossy fibers during kainic acid-induced seizures, a histofluorescence study. Brain Res 446, 383–386.

    Article  PubMed  CAS  Google Scholar 

  • Frederickson CJ, Hernandez MD, McGinty JF. 1989 Translocation of zinc may contribute to seizure-induced death of neurons. Brain Res 480, 317–321.

    Article  PubMed  CAS  Google Scholar 

  • Frederickson CJ, Kasarskis EJ, Ringo D, Frederickson RE. 1987a A quinoline fluorescence method for visualizing and assaying the histochemically-reactive zinc in the brain. J Neurosci Meth 20, 91–103.

    Article  CAS  Google Scholar 

  • Frederickson CJ, Klitenick MA, Manton WI, Kirkpatrick JB. 1983 Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat. Brain Res 273, 335–339.

    Article  PubMed  CAS  Google Scholar 

  • Frederickson CJ, Moncrieff DW. 1994 Zinc-containing neurons. Biol Signals 3, 127–139.

    Article  PubMed  CAS  Google Scholar 

  • Frederickson CJ, Perez-Clausell J, Danscher G. 19876 Zinc-Containing 7S-NGF Complex, Evidence from Zinc Histochemistry for Localization in Salivary Secretory Granules. J Histochem Cytochem 35, 579–583.

    Google Scholar 

  • Frederickson CJ, Rampy BA, Reamy-Rampy S, Howell GA. 1992 Distribution of histochemically reactive zinc in the forebrain of the rat. J Chem Neuroanat 5, 521–530.

    Article  PubMed  CAS  Google Scholar 

  • Frederickson CJ, Suh SW, Cha K, Koh JY, Cuajungco MP. 200 lb Depletion of Intracellular Zinc in Neurons by Use of an Extra-cellular Chelator in vivo and in vitro. Neuroreport (in press).

    Google Scholar 

  • Frederickson CJ, Suh SW, Silva D, Frederickson CJ, Thompson RB. 2000 Importance of zinc in the central nervous system, the zinc-containing neuron. J Nutr 130 (Suppl 5), 14715–14835.

    Google Scholar 

  • Griffin WST, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White III CL, Araoz C. 1989 Brain interleukin-1 and S-100b immunoreactivity are elevated in Down syndrome and Alzheimer’s disease. Proc Natl Acad Sci USA 86, 7611–7615.

    Article  PubMed  CAS  Google Scholar 

  • Haug F-MS. 1967 Electron microscopical localization of the zinc in hippocampal, mossy fiber synapses by a modified sulfide silver procedure. Histochemie 8, 355–368.

    Article  PubMed  CAS  Google Scholar 

  • Herwald H, Morgelin M, Svensson HG, Sjobring U. 2001 Zinc-dependent conformational changes in domain D5 of high molecular mass kininogen modulate contact activation. Eur J Biochem 268, 396–404.

    Article  PubMed  CAS  Google Scholar 

  • Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa, RC, Cuajungco MP, Gray DN, Lim J, Moir RD, Tanzi RE, Bush AI. 1999a The Aß peptide of Alzheimer’s Disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38, 7609–7616.

    Article  PubMed  CAS  Google Scholar 

  • Huang X, Atwood CS, Moir RD, Hartshorn MA, Vonsattel JP, Tanzi RE, Bush AI. 1997 Zinc-induced Alzheimer’s Abetal-40 aggregation is mediated by conformational factors. J Biol Chem 272, 26464–26470.

    Article  PubMed  CAS  Google Scholar 

  • Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall J, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa, RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI. 1999b Cu(II) potentiation of Alzheimer Aß neurotoxicity, correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 274, 37111–37116.

    Article  PubMed  CAS  Google Scholar 

  • Hughes SR, Khorkova O, Goyal S, Knaeblein J, Heroux J, Riedel NG, Sahasrabudhe S. 1998 a2-Macroglobulin associates with ßamyloid peptide and prevents fibril formation. Proc Natl Acad Sci USA 95, 3275–3280.

    Google Scholar 

  • Hyun HJ, Sohn J, Ahn YH, Shin HC, Koh JY, Yoon YH. 2000 Depletion of intracellular zinc induces macromolecule synthesis-and caspase-dependent apoptosis of cultured retinal cells. Brain Res 869, 39–48.

    Article  PubMed  CAS  Google Scholar 

  • Keizer J, Levine L. 1996 Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. Biophys J 71, 3477–3487.

    Article  PubMed  CAS  Google Scholar 

  • Koh JY, Suh SW, Gwag BJ, He YY, Hsu CY, Choi DW. 1996 The role of zinc in selective neuronal death after transient global cerebral ischemia. Science 272, 1013–1016.

    Article  PubMed  CAS  Google Scholar 

  • Kovacs KJ, Larson AA. 1997 Zn2+ inhibition of [3H]MK-801 binding is different in mouse brain and spinal cord, effect of glycine and glutamate. Eur J Pharmacol 324, 117–123.

    Article  PubMed  CAS  Google Scholar 

  • Land PW, Akhtar ND. 1999 Experience-dependent alteration of synaptic zinc in rat somatosensory barrel cortex. Somatosens Mot Res 16, 139–150.

    Article  PubMed  CAS  Google Scholar 

  • Lee JY, Cole TB, Palmiter RD, Koh JY. 2000 Accumulation of zinc in degenerating hippocampal neurons of ZnT3-null mice after seizures, evidence against synaptic vesicle origin. J Neurosci 1(20), RC79.

    Google Scholar 

  • Lee J-Y, Mook-Jung I, Koh J-Y. 1999 Histochemically reactive zinc in plaques of the Swedish mutant beta-amyloid precursor protein transgenic mice. J Neurosc 19 (10), l-5.

    Google Scholar 

  • Lees GJ, Cuajungco MP, Leong W. 1998 Effect of metal chelating agents on the direct and seizure-related neuronal death induced by zinc and kainic acid. Brain Res 799, 108–117.

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Hough C, Suh SW, Sarvey J, Frederickson CJ. 2001a Evidence that Synaptically-released Zn2+ is translocated into postsynaptic neuons during synaptic transmission. J Neurophysiol (in press).

    Google Scholar 

  • Li Y, Hough C, Frederickson CJ, Sarvey JA. 200lb Zinc release and entry into pre-and postsynaptic neurons is required for LTP in the mossy fiber-CA3 synapse. Soc Neurosci Abs (in press).

    Google Scholar 

  • Lobner D, Canzoniero LM, Manzerra P, Gottron F, Ying H, Knudson M, Tian M, Dugan LL, Kerchner GA, Sheline CT, Korsmeyer SJ, Choi DW. 2000 Zinc-induced neuronal death in cortical neurons. Cell Mol Biol 46, 797–806.

    PubMed  CAS  Google Scholar 

  • Long YY, Frederickson CJ. 1994 A Zinc-Containing Fiber System of Thalamic Origin. NeuroReport 5, 2026–2028.

    CAS  Google Scholar 

  • Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. 1998 Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 158, 47–52.

    Article  PubMed  CAS  Google Scholar 

  • Maret W. 2000 The function of zinc metallothionein, a link between cellular zinc and redox state. J Nutr 130 (Suppl 5), 1455S - 1458S.

    PubMed  CAS  Google Scholar 

  • Marshak DR, Pesce SA, Stanley LC, Griffin WST. 1991 Increased 5–100b neurotrophic activity in Alzheimer’s disease temporal lobe. Neurobiol Aging 13, 1–7.

    Article  Google Scholar 

  • Maske H. 1955 Uber den topochemischen Nachweis von Zink in Ammonshorn verschiedener Säugetiere. Naturwissenschaften 42, 424.

    Article  CAS  Google Scholar 

  • McLardy T. 1970 Anatomical rationale of ablative surgery for temporal lobe seizures and dyscontrol, suggested stereo-chemode chelate-blockade alternative. Acta Neurochir 23, 119–124.

    Google Scholar 

  • McLean C, Cherny R, Fraser F, Fuller S, Smith M, Beyreuther K, Bush A, Masters C. 1999 Soluble pool of Aß amyloid as a determinant of severity of neurodegeneration in Alzheimer’s. Disease Ann Neurol 46, 860–966.

    Article  CAS  Google Scholar 

  • Melamed-Book N, Kachalsky SG, Kaiserman I, Rahamimoff R. 1999 Neuronal calcium sparks and intracellular calcium ‘noise’. Proc Natl Acad Sci USA 96, 15217–15221.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell C, Barnes M. 1993 Proconvulsant action of diethyldithiocarbamate in stimulation of the perforant path. Neurotox Teratol 15, 165–171.

    Article  CAS  Google Scholar 

  • Morton JD, Howell GA, Frederickson CJ. 1990 Effects of subcutaneous injections of zinc chloride on seizures induced by noise and by kainic acid. Epilepsia 31, 139–144.

    Article  PubMed  CAS  Google Scholar 

  • Morvan J, Hunter D-F, Krause L, Flinn JM, Jones BF. 2000 Synchrotron X-ray fluorescence demonstrates increased zinc in the cortex of rats raised on drinking water containing enhanced levels of zinc. Soc Neurosci Abs.

    Google Scholar 

  • Palmiter RD, Cole TB, Quaife CF, Findley SD. 1996 ZnT-3, a putative transporter of zinc into synaptic vesicles. Proc Natl Acad Sci USA 93, 14934–14939.

    Article  PubMed  CAS  Google Scholar 

  • Pattison SE, Dunn MF. 1976a On the mechanism of divalent metal ion chelator induced activation of the 7S nerve growth factor esteropeptidase, activation by 2,2’,2“-terpyridine and by 8hydroxyquinoline-5-sulfonic acid. Biochemistry 15, 3691–3696.

    Article  PubMed  CAS  Google Scholar 

  • Pattison SE, Dunn MF. 1976b On the mechanism of divalent metal ion chelator induced activation of the 7S nerve growth factor esteropeptidase, thermodynamics and kinetics of activation. Biochemistry 15, 3696–3703.

    Article  PubMed  CAS  Google Scholar 

  • Powell JJ, Burden TJ, Greenfield SM, Taylor PD, Thompson RP. 1999 Urinary excretion of essential metals following intravenous calcium disodium edetate, an estimate of free zinc and zinc status in man. J lnorg Biochem 75, 159–165.

    Article  CAS  Google Scholar 

  • Prough DS, Suh SW, Frederickson CJ, Li ZY, DeWitt DS. 2001 Traumatic brain injury and hemorrhagic hypotension increase cortical and hippocampal zinc translocation in rats. Crit Care Med 28 (76, Supplement S).

    Google Scholar 

  • Qian WJ, Aspinwall CA, Battiste MA, Kennedy RT. 2000 Detection of secretion from single pancreatic beta-cells using extracellular fluorogenic reactions and confocal fluorescence microscopy. Anal Chem 72, 711–717.

    Article  PubMed  CAS  Google Scholar 

  • Roher AE, Kasunic TC, Woods AS, Cotter RJ, Ball MJ, Fridman R. 1994 Proteolysis of Aß peptide from Alzheimer’s disease brain by gelatinase A. Biochem Biophys Res Commun 205, 1755–1761.

    Article  PubMed  CAS  Google Scholar 

  • Ross GM, Shamovsky IL, Lawrence G, Solc M, Dostaler SM, Jimmo SL, Weaver DF, Riopelle RJ. 1997 Zinc alters conformation and inhibits biological activities of nerve growth factor and related neurotrophins. Nat Med 8, 872–878.

    Article  Google Scholar 

  • Rubio ME, Juiz JM. 1998 Chemical anatomy of excitatory endings in the dorsal cochlear nucleus of the rat, differential synaptic distribution of aspartate aminotransferase, glutamate, and vesicular zinc. J Comp Neural 399, 341–358.

    Article  CAS  Google Scholar 

  • Shivers BD, Hilbich C, Multhaup G, Salbaum M, Beyreuther K, Seeburg PH. 1988 Alzheimer’s disease amyloidogenic glycoprotein, expression pattern in rat brain suggests role in cell contact. EMBO J. 7, 1365–1370.

    PubMed  CAS  Google Scholar 

  • Simons TJ. 1991 Intracellular free zinc and zinc buffering in human red blood cells. J Membr Biol 123, 63–71.

    Article  PubMed  CAS  Google Scholar 

  • Smart TG, Xie X, Krishek BJ. 1994 Modulation of inhibitory and excitatory amino acids receptor ion channels by zinc. Prog Neurobiol 42, 393–441.

    Article  PubMed  CAS  Google Scholar 

  • Sorensen J, Mattson B, Andreasen A, Johansson B. 1998 Rapid disappearance of zinc positive terminals in focal brain ischemia. Brain Res 812, 265–269.

    Article  PubMed  CAS  Google Scholar 

  • Suh SW, Chen JW, Motamedi M, Bell B, Listiak K, Pons NF, Danscher G, Frederickson CJ. 2000a Evidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury. Brain Res 852, 268–273.

    Article  PubMed  CAS  Google Scholar 

  • Suh SW, Frederickson CJ. 2001 Loss of vesicular zinc and appearance of perikaryal zinc after seizures induced by pilocarpine. NeuroReport 12, 1523–1525.

    CAS  Google Scholar 

  • Suh SW, Jensen KB, Jensen MS, Silva DS, Kesslak PJ, Dan-scher G, Frederickson CJ. 2000b Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer’s diseased brains. Brain Res 852, 274–278.

    Article  PubMed  CAS  Google Scholar 

  • Suh SW, Thompson RB, Zeng YA, Hough C, Li Y, Sarvey J, Frederickson CJ. 2001 Zinc signals in apical dendrites after stimulation of zinc-containing (but not zinc-free) synaptic inputs. Soc Neurosci Abs (in press).

    Google Scholar 

  • Thompson RB, Whetsell WO, Maliwal BP, Fierke CA, Frederickson CJ. 2000 Fluorescence Microscopy of stimulated Zn(II) release from organotypic cultures of mammalian hippocampus using a carbonic anhydrase-based biosensor system. J Neurosci Meth 96, 35–45.

    Article  CAS  Google Scholar 

  • Thompson RB, Suh SW, Fierke C, Frederickson CJ. 2001 Ratio-metric quantitation of fast Zn2+ signals in the brain. SPIE (in press).

    Google Scholar 

  • Tonder N, Johansen FF, Frederickson CJ, Zimmer J, Diemer NH. 1990 Possible role of zinc in the selective degeneration of dentate hilar neurons after cerebral ischemia in the adult rat. Neurosci Lett 109, 247–252.

    Article  PubMed  CAS  Google Scholar 

  • Toutenhoofd SL, Strehler EE. 2000 The calmodulin multigene family as a unique case of genetic redundancy, multiple levels of regulation to provide spatial and temporal control of calmodulin pools? Cell Calcium 28, 83–96.

    Article  PubMed  CAS  Google Scholar 

  • Truong-Tran AQ, Carter J, Ruffin R, Zalewski PD. 2001 New insights into the role of zinc in the respiratory epithelium. Immunol Cell Biol 79, 170–177.

    Article  PubMed  CAS  Google Scholar 

  • Vallee BL, Falchuk KH. 1993 The biochemical basis of zinc physiology. Physiol Rev 73, 79–118.

    Article  PubMed  CAS  Google Scholar 

  • Van Assche F, van Tilborg W, Waeterschoot H. 1996 Environmental Risk Assessment for Essential Elements - Case Study Zinc. In: `Report of the International Workshop on Risk Assessment of Metals and their Inorganic Compounds’ Ottawa: ICME; 171–180.

    Google Scholar 

  • Vincent SR, Semba KA. 1989 A heavy metal marker of the developing striatal mosaic. Dey Brain Res 45, 155–159.

    Article  CAS  Google Scholar 

  • Vogt K, Mellor J, Tong G, Nicoll R. 2000 The actions of synaptically released zinc at hippocampal mossy fiber synapses. Neuron 26, 187–196.

    Article  PubMed  CAS  Google Scholar 

  • Walker MC, Ruiz A, Kullmann DM. 2001 Monosynaptic GABAergic Signaling from Dentate to CA3 with a Pharmacological and Physiological Profile Typical of Mossy Fiber Synapses. Neuron 29, 703–715.

    Article  PubMed  CAS  Google Scholar 

  • Weiss JH, Sensi SL, Koh JY. 2000 Zn(2+), a novel ionic mediator of neural injury in brain disease. Trends Pharmacol Sci 10, 39540 I.

    Google Scholar 

  • Weiss JH, Sensi SL. 2000 Ca2+-Zn2+ permeable AMPA or kainate receptors, possible key factors in selective neurodegeneration. Trends Neurosci 20, 365–371.

    Article  Google Scholar 

  • Williams, RJP. 1996 Calcium binding proteins in normal and transformed cells. Cell Calcium 20, 87–93.

    Article  PubMed  CAS  Google Scholar 

  • Ye B, Maret W, Vallee BL. 2001 Zinc metallothionein imported into liver mitochondria modulates respiration. Proc Natl Acad Sci USA 98, 2317–2322.

    Article  PubMed  CAS  Google Scholar 

  • Yoon YH, Jung KH, Sadun AA, Shin HC, Koh JY, Park JA, Lee JY, Sato TA, Koh JY. 2000 Co-induction of p75NTR and p75NTRassociated death executor in neurons after zinc exposure in cortical culture or transient ischemia in the rat. Neurosci 20, 9096–9103.

    Google Scholar 

  • Zambenedetti P, Giordano R, Zatta, P. 1998 Metallothioneins are highly expressed in astrocytes and microcapillaries in Alzheimer’s disease. J Chem Neuroanat 15, 21–26.

    Article  PubMed  CAS  Google Scholar 

  • Zangger K, Oz G, Haslinger E, Kunert O, Armitage IM. 2001 Nitric oxide selectively releases metals from the N-terminal domain of metallothioneins, potential role at inflammatory sites. FASEB J 15, 1303–1305.

    PubMed  CAS  Google Scholar 

  • ZhuGe R, Fogarty KE, Tuft RA, Lifshitz LM, Sayar K, Walsh JV Jr. 2000 Dynamics of signaling between Ca(2+) sparks and Ca(2+)- activated K(+) channels studied with a novel image-based method for direct intracellular measurement of ryanodine receptor Ca(2+) current. J Gen Physiol 16, 845–864.

    Article  Google Scholar 

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  1. NeuroBioTex, Inc., Biomedical Engineering and Anatomy and Neuroscience, The University of Texas Medical Branch, Galveston, Texas, USA

    Christopher J. Frederickson

  2. Laboratory for Oxidation Biology, Harvard Medical School, Boston, Massachusetts, USA

    Ashley I. Bush

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  1. Christopher J. Frederickson
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  2. Ashley I. Bush
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  1. Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA, USA

    W. Maret

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Frederickson, C.J., Bush, A.I. (2001). Synaptically released zinc: Physiological functions and pathological effects. In: Maret, W. (eds) Zinc Biochemistry, Physiology, and Homeostasis. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-3728-9_10

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  • DOI: https://doi.org/10.1007/978-94-017-3728-9_10

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