Synaptic release of zinc from brain slices: Factors governing release, imaging, and accurate calculation of concentration

Frederickson, Christopher J.; Giblin, Leonard J.; Balaji, Ramachandran; Masalha, Rafik; Frederickson, C.J.; Zeng, Yaping; Varea, Emilio; Koh, Jae‐Young; Chorin, Udi; Besser, Limor; Hershfinkel, Michal; Li, Yang; Thompson, Richard B.; Krężel, Artur

doi:10.1016/j.jneumeth.2005.11.014

Cited by 111 publications

(96 citation statements)

References 49 publications

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“…The build-up of zinc progressively increases inhibition of kainate receptors. This conclusion is in agreement with studies using a variety of techniques, including fluorescent zinc indicators that have found increased zinc concentrations in the microenvironment of mossy fiber terminals after mossy fiber stimulation (Assaf and Chung, 1984;Howell et al, 1984;Li et al, 2001b;Ueno et al, 2002;QuintaFerreira et al, 2004;Frederickson et al, 2005Frederickson et al, , 2006a (Smart et al, 1994), and glycine (Bloomenthal et al, 1994;Laube et al, 1995;Hirzel et al, 2006). The ability of zinc chelators to influence the function of these receptors provides strong support for the activity dependent release of zinc at synapses.…”

Section: Role Of Zinc In Synaptic Physiologysupporting

confidence: 85%

“…We used zinc chelators to test whether endogenously released zinc regulates kainate receptor-mediated fEPSPs at mossy fiber synapses. Zinc in mossy fiber boutons appears approximately synchronously with the developmental appearance of granule neurons (Frederickson et al, 2006a). According to Frederickson et al (2006a), young rat pups (16 d old) have little synaptic zinc.…”

Section: Endogenous Zinc Limits Frequency Facilitation Of Mossy-fibermentioning

confidence: 99%

“…Zinc in mossy fiber boutons appears approximately synchronously with the developmental appearance of granule neurons (Frederickson et al, 2006a). According to Frederickson et al (2006a), young rat pups (16 d old) have little synaptic zinc. As granule neurons develop and mossy fiber axons mature, increasing levels of zinc can be detected.…”

Section: Endogenous Zinc Limits Frequency Facilitation Of Mossy-fibermentioning

confidence: 99%

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pH-Dependent Inhibition of Kainate Receptors by Zinc

Mott¹,

Benveniste²,

Dingledine³

2008

J. Neurosci.

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Kainate receptors contribute to synaptic plasticity and rhythmic oscillatory firing of neurons in corticolimbic circuits including hippocampal area CA3. We use zinc chelators and mice deficient in zinc transporters to show that synaptically released zinc inhibits postsynaptic kainate receptors at mossy fiber synapses and limits frequency facilitation of kainate, but not AMPA EPSCs during thetapattern stimulation. Exogenous zinc also inhibits the facilitatory modulation of mossy fiber axon excitability by kainate but does not suppress the depressive effect of kainate on CA3 axons. Recombinant kainate receptors are inhibited in a subunit-dependent manner by physiologically relevant concentrations of zinc, with receptors containing the KA1 subunit being sensitive to submicromolar concentrations of zinc. Zinc inhibition does not alter receptor desensitization nor apparent agonist affinity and is only weakly voltage dependent, which points to an allosteric mechanism. Zinc inhibition is reduced at acidic pH. Thus, in the presence of zinc, a fall in pH potentiates kainate receptors by relieving zinc inhibition. Acidification of the extracellular space, as occurs during repetitive activity, may therefore serve to unmask kainate receptor neurotransmission. We conclude that zinc modulation of kainate receptors serves an important role in shaping kainate neurotransmission in the CA3 region.

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Section: Role Of Zinc In Synaptic Physiologysupporting

confidence: 85%

Section: Endogenous Zinc Limits Frequency Facilitation Of Mossy-fibermentioning

confidence: 99%

Section: Endogenous Zinc Limits Frequency Facilitation Of Mossy-fibermentioning

confidence: 99%

See 1 more Smart Citation

pH-Dependent Inhibition of Kainate Receptors by Zinc

Mott¹,

Benveniste²,

Dingledine³

2008

J. Neurosci.

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“…The Zn 2+ that aggregates Aβ in vivo is released from synaptic vesicles of glutamatergic neurons during neurotransmission reaching an extracellular concentration of 300 µM (Frederickson et al, 2006). It is normally transferred into glutamatergic presynaptic vesicles by the activity of ZnT3, a transmembrane protein which expression overlaps with brain regions where amyloid depositions are the most frequent (Palmiter et al, 1996, Stoltenberg et al, 2007.…”

Section: Impaired Zn 2+ Homeostasis In Admentioning

confidence: 99%

“…The reasons for extracellular Zn 2+ precipitation of Aβ with age, when both are constitutively released with synaptic activity (Lazarov et al, 2002, Frederickson et al, 2006, Cirrito et al, 2008, are unresolved. We utilized acute hippocampal slices to model Zn 2+ release throughout the neocortex (since ZnT3 is expressed in both area)), and to study changes that occur with age and gender that may explain how these risk factors affect Alzheimer pathology.…”

Section: Impaired Zn 2+ Homeostasis In Admentioning

confidence: 99%

Physiological factors could enhance amyloid-beta toxicity

Gábor¹

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Involvement of N‐methyl‐D‐aspartate receptor subunits in zinc‐mediated modification of CA1 long‐term potentiation in the developing hippocampus

Takeda

Itagaki

Ando

et al. 2011

J of Neuroscience Research

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Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 μM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 μM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus.

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Synaptic release of zinc from brain slices: Factors governing release, imaging, and accurate calculation of concentration

Cited by 111 publications

References 49 publications

pH-Dependent Inhibition of Kainate Receptors by Zinc

pH-Dependent Inhibition of Kainate Receptors by Zinc

Physiological factors could enhance amyloid-beta toxicity

Involvement of N‐methyl‐D‐aspartate receptor subunits in zinc‐mediated modification of CA1 long‐term potentiation in the developing hippocampus

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