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Mechanisms of Zn 2+ efflux in cultured cortical neurons
Author(s) -
Qin Yan,
Thomas Dustin,
Fontaine Charles P.,
Colvin Robert A.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05700.x
Subject(s) - efflux , extracellular , intracellular , biophysics , chemistry , zinc , homeostasis , transporter , biochemistry , microbiology and biotechnology , biology , organic chemistry , gene
Zinc dyshomeostasis in brain might be involved in the pathogenesis of brain diseases such as Alzheimer’s disease and stroke. Resting neurons tightly regulate and maintain low to subnanomolar levels of intracellular free Zn 2+ , but mechanisms of normal Zn 2+ homeostasis are poorly understood. In this study, the mechanisms of transporter‐mediated Zn 2+ extrusion across the plasma membrane of cultured cortical neurons were studied. Changes in intracellular free Zn 2+ levels were tracked in individual neurons by microfluorometry using a Zn 2+ selective fluorophore, FluoZin3. Unopposed Zn 2+ efflux was measured by first loading cultured cortical neurons with Zn 2+ then reducing extracellular Zn 2+ to near zero by addition of EDTA. Studies revealed that the primary means of Zn 2+ efflux in cortical neurons required both extracellular Na + and Ca 2+ . The actions of either Na + or Ca 2+ on Zn 2+ efflux were blunted in the absence of the other cation. Reversed Na + gradients could induce Zn 2+ uptake. The Na + dependence of Zn 2+ efflux was not affected by a small pH o shift (7.6–8); whereas an effect of Ca 2+ was not observed at pH o 8. In summary, a Na + , Ca 2+ /Zn 2+ exchanger mechanism is proposed to be the primary transport mechanism that extrudes Zn 2+ when neuronal intracellular free Zn 2+ levels rise.