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Routes of zinc entry in mouse cortical neurons: role in zinc‐induced neurotoxicity
Author(s) -
Marin Philippe,
Israël Maurice,
Glowinski Jacques,
Prémont Joël
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00875.x
Subject(s) - nmda receptor , ampa receptor , glutamate receptor , neurotoxicity , chemistry , biophysics , depolarization , receptor , biochemistry , biology , toxicity , organic chemistry
Exposure of central neurons to Zn 2+ triggers neuronal death. The routes of Zn 2+ entry were investigated in living cortical neurons from the mouse using the specific Zn 2+ fluorescent dye N‐(6‐methoxy‐8‐quinolyl)‐p‐toluene sulphonamide (TSQ), which preferentially detects membrane‐bound Zn 2+. Exposure of cortical neurons to increasing concentrations of Zn 2+ (1–100 μ m ) induced a progressive increase in the fluorescence of TSQ. This fluorescence signal was not attenuated by the permeation of plasma membrane with digitonin. Accordingly, the major part of TSQ fluorescence (two‐thirds) was associated to the particulate fraction of cortical neurons exposed to Zn 2+. These results suggest that Zn 2+ detected with TSQ in neurons is mainly bound to membranes. TSQ fluorescence measured in neurons exposed to 3 μ m Zn 2+ was enhanced by Na + ‐pyrithione, a Zn 2+ ionophore, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), N‐methyl‐ d ‐aspartate (NMDA) or KCl‐induced depolarization. However, in the absence of any treatment, TSQ labelling of neurons exposed to 3 μ m Zn 2+ was only decreased by NMDA receptor antagonists, whereas it remained unaltered in the presence of antagonists of AMPA receptors or L‐type voltage‐gated Ca 2+ channels. Zn 2+ entry through NMDA receptors did not contribute to Zn 2+ ‐induced neuronal death, as it was prevented by antagonists of NMDA receptors only when they were added after the Zn 2+ exposure. Finally, Zn 2+ induced a delayed accumulation of extracellular glutamate which might be responsible for the delayed NMDA receptor activation that leads to neuronal death.