DOI: 10.1046/j.1460-9568.2000.00277.x. AMPA/kainate receptor‐triggered Zn<sup>2+</sup> entry into cortical neurons induces mitochondrial Zn<sup>2+</sup> uptake and persistent mitochondrial dysfunction

AMPA/kainate receptor‐triggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction

10.1046/j.1460-9568.2000.00277.x

Crossref journal-article

Wiley

European Journal of Neuroscience (311)

Abstract

AbstractRapid Zn2+ influx through Ca2+‐permeable AMPA/kainate (Ca‐A/K) channels triggers reactive oxygen species (ROS) generation and is potently neurotoxic. The first aim of this study was to determine whether these effects might result from direct mitochondrial Zn2+ uptake. Adapting the mitochondrially sequestered divalent cation sensitive probe, rhod‐2, to visualize mitochondrial Zn2+, present studies indicate that Zn2+ is taken up into these organelles. The specificity of the signal for Zn2+ was indicated by its reversal by Zn2+ chelation, and its mitochondrial origin indicated by its speckled extranuclear appearance and by its elimination upon pretreatment with the mitochondrial protonophore, carbonyl cyanide p‐(trifluoromethoxy)phenylhydrazone (FCCP). Consistent with inhibition of mitochondrial Zn2+ uptake, FCCP also slowed the recovery of cytosolic Zn2+ elevations in Ca‐A/K(+) neurons. Further studies sought clues to the high toxic potency of intracellular Zn2+. In experiments using the mitochondrial membrane polarization (ΔΨm)‐sensitive probe tetramethylrhodamine ethyl ester and the ROS‐sensitive probe hydroethidine, brief kainate exposures in the presence of 300 μm Zn2+ (with or without Ca2+) resulted in prolonged loss of ΔΨm and corresponding prolonged ROS generation in Ca‐A/K(+) neurons, in comparison to the more rapid recovery from loss of ΔΨm and transient ROS generation after kainate/1.8 mm Ca2+ exposures.

Bibliography

Sensi, S. L., Yin, H. Z., & Weiss, J. H. (2000). AMPA/kainate receptorâtriggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction. European Journal of Neuroscience, 12(10), 3813â3818. Portico.

Authors 3

Stefano L. Sensi (first)
Hong Z. Yin (additional)
John H. Weiss (additional)

References 30 Referenced 133

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{'key': 'e_1_2_6_18_1', 'first-page': '974', 'article-title': 'Privileged access to mitochondria of calcium influx through N‐methyl‐d‐aspartate receptors', 'volume': '53', 'author': 'Peng T.I.', 'year': '1998', 'journal-title': 'Mol. Pharmacol.'} / Mol. Pharmacol. / Privileged access to mitochondria of calcium influx through N‐methyl‐d‐aspartate receptors by Peng T.I. (1998)
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Dates

Type	When
Created	22 years, 5 months ago (March 6, 2003, 9:27 a.m.)
Deposited	1 year, 11 months ago (Oct. 3, 2023, 4:16 p.m.)
Indexed	1 month, 4 weeks ago (July 7, 2025, 12:38 p.m.)
Issued	24 years, 11 months ago (Oct. 1, 2000)
Published	24 years, 11 months ago (Oct. 1, 2000)
Published Online	23 years, 8 months ago (Dec. 24, 2001)
Published Print	24 years, 11 months ago (Oct. 1, 2000)

Funders 0

None

BibTeX

@article{Sensi_2000, title={AMPA/kainate receptor‐triggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction}, volume={12}, ISSN={1460-9568}, url={http://dx.doi.org/10.1046/j.1460-9568.2000.00277.x}, DOI={10.1046/j.1460-9568.2000.00277.x}, number={10}, journal={European Journal of Neuroscience}, publisher={Wiley}, author={Sensi, Stefano L. and Yin, Hong Z. and Weiss, John H.}, year={2000}, month=oct, pages={3813–3818} }

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