Depolarization-Induced 65Zinc Influx into Cultured Cortical Neurons
Toxic Zn2+ influx may be a key mechanism underlying selective neuronal death after transient global ischemia in rats. To identify routes responsible for neuronal Zn2+ influx, we measured the accumulation of 65Zn2+ into cultured murine cortical cells under depolarizing conditions (60 mM K+) associate...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2002-06-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996102904973 |
| _version_ | 1819119481095454720 |
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| author | Christian T. Sheline Howard S. Ying Chris S. Ling Lorella M.T. Canzoniero Dennis W. Choi |
| author_facet | Christian T. Sheline Howard S. Ying Chris S. Ling Lorella M.T. Canzoniero Dennis W. Choi |
| author_sort | Christian T. Sheline |
| collection | DOAJ |
| description | Toxic Zn2+ influx may be a key mechanism underlying selective neuronal death after transient global ischemia in rats. To identify routes responsible for neuronal Zn2+ influx, we measured the accumulation of 65Zn2+ into cultured murine cortical cells under depolarizing conditions (60 mM K+) associated with severe hypoxia-ischemia in brain tissue. Addition of 60 mM K+ or 300 μM kainate substantially increased 65Zn2+ accumulation into mixed cultures of neurons and glia, but not glia alone. 65Zn2+ accumulation was attenuated by increasing concentrations of extracellular Ca2+ or trypsin pretreatment, but not by late trypsinization, and corresponded to an increase in atomic Zn2+. Confirming predominantly neuronal entry, K+-induced 65Zn2+ accumulation was reduced by prior selective destruction of neurons with NMDA. K+-induced 65Zn2+ influx was not sensitive to glutamate receptor antagonists, but was attenuated by Gd3+ and Cd2+ as well as 1 μM nimodipine; it was partially sensitive to 1 μM ω-conotoxin-GVIA, and insensitive to 1 μM ω-agatoxin-IVA. K+-induced, Gd3+-sensitive 45Ca2+ accumulation but not 65Zn2+ accumulation was sharply attenuated by lowering extracellular pH to 6.6. |
| first_indexed | 2024-12-22T06:05:27Z |
| format | Article |
| id | doaj.art-1a80e09609dc441db866f3c256b0c521 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T06:05:27Z |
| publishDate | 2002-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-1a80e09609dc441db866f3c256b0c5212022-12-21T18:36:26ZengElsevierNeurobiology of Disease1095-953X2002-06-011014153Depolarization-Induced 65Zinc Influx into Cultured Cortical NeuronsChristian T. Sheline0Howard S. Ying1Chris S. Ling2Lorella M.T. Canzoniero3Dennis W. Choi4Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110; Monsanto Corporation, Monsanto Corporation Research Division, 800 North Lindberg Avenue, St. Louis, Missouri, 63167Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110; Monsanto Corporation, Monsanto Corporation Research Division, 800 North Lindberg Avenue, St. Louis, Missouri, 63167Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110; Monsanto Corporation, Monsanto Corporation Research Division, 800 North Lindberg Avenue, St. Louis, Missouri, 63167Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110; Monsanto Corporation, Monsanto Corporation Research Division, 800 North Lindberg Avenue, St. Louis, Missouri, 63167Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri, 63110; Monsanto Corporation, Monsanto Corporation Research Division, 800 North Lindberg Avenue, St. Louis, Missouri, 63167Toxic Zn2+ influx may be a key mechanism underlying selective neuronal death after transient global ischemia in rats. To identify routes responsible for neuronal Zn2+ influx, we measured the accumulation of 65Zn2+ into cultured murine cortical cells under depolarizing conditions (60 mM K+) associated with severe hypoxia-ischemia in brain tissue. Addition of 60 mM K+ or 300 μM kainate substantially increased 65Zn2+ accumulation into mixed cultures of neurons and glia, but not glia alone. 65Zn2+ accumulation was attenuated by increasing concentrations of extracellular Ca2+ or trypsin pretreatment, but not by late trypsinization, and corresponded to an increase in atomic Zn2+. Confirming predominantly neuronal entry, K+-induced 65Zn2+ accumulation was reduced by prior selective destruction of neurons with NMDA. K+-induced 65Zn2+ influx was not sensitive to glutamate receptor antagonists, but was attenuated by Gd3+ and Cd2+ as well as 1 μM nimodipine; it was partially sensitive to 1 μM ω-conotoxin-GVIA, and insensitive to 1 μM ω-agatoxin-IVA. K+-induced, Gd3+-sensitive 45Ca2+ accumulation but not 65Zn2+ accumulation was sharply attenuated by lowering extracellular pH to 6.6.http://www.sciencedirect.com/science/article/pii/S0969996102904973global ischemianeuronal deathexcitotoxicitycalcium channelsglutamate |
| spellingShingle | Christian T. Sheline Howard S. Ying Chris S. Ling Lorella M.T. Canzoniero Dennis W. Choi Depolarization-Induced 65Zinc Influx into Cultured Cortical Neurons Neurobiology of Disease global ischemia neuronal death excitotoxicity calcium channels glutamate |
| title | Depolarization-Induced 65Zinc Influx into Cultured Cortical Neurons |
| title_full | Depolarization-Induced 65Zinc Influx into Cultured Cortical Neurons |
| title_fullStr | Depolarization-Induced 65Zinc Influx into Cultured Cortical Neurons |
| title_full_unstemmed | Depolarization-Induced 65Zinc Influx into Cultured Cortical Neurons |
| title_short | Depolarization-Induced 65Zinc Influx into Cultured Cortical Neurons |
| title_sort | depolarization induced 65zinc influx into cultured cortical neurons |
| topic | global ischemia neuronal death excitotoxicity calcium channels glutamate |
| url | http://www.sciencedirect.com/science/article/pii/S0969996102904973 |
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