Depolarization-induced 65zinc influx into cultured cortical neurons.

Toxic Zn(2+) influx may be a key mechanism underlying selective neuronal death after transient global ischemia in rats. To identify routes responsible for neuronal Zn(2+) influx, we measured the accumulation of (65)Zn(2+) 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 microM kainate substantially increased (65)Zn(2+) accumulation into mixed cultures of neurons and glia, but not glia alone. (65)Zn(2+) accumulation was attenuated by increasing concentrations of extracellular Ca(2+) or trypsin pretreatment, but not by late trypsinization, and corresponded to an increase in atomic Zn(2+). Confirming predominantly neuronal entry, K(+)-induced (65)Zn(2+) accumulation was reduced by prior selective destruction of neurons with NMDA. K(+)-induced (65)Zn(2+) influx was not sensitive to glutamate receptor antagonists, but was attenuated by Gd(3+) and Cd(2+) as well as 1 microM nimodipine; it was partially sensitive to 1 microM omega-conotoxin-GVIA, and insensitive to 1 microM omega-agatoxin-IVA. K(+)-induced, Gd(3+)-sensitive (45)Ca(2+) accumulation but not (65)Zn(2+) accumulation was sharply attenuated by lowering extracellular pH to 6.6. 2002 Elsevier Science (USA).