Depolarization-induced 65zinc influx into cultured cortical neurons

Christian T. Sheline, Howard S. Ying, Chris S. Ling, Lorella M.T. Canzoniero, Dennis W. Choi

Research output: Contribution to journalArticlepeer-review


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 K6) 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.

Original languageEnglish (US)
Pages (from-to)41-53
Number of pages13
JournalNeurobiology of Disease
Issue number1
StatePublished - 2002


  • Calcium channels
  • Excitotoxicity
  • Global ischemia
  • Glutamate
  • Neuronal death

ASJC Scopus subject areas

  • Neurology


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