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.
Sheline
Christian T
CT
Center for the Study of Nervous System Injury, Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Ying
Howard S
HS
Ling
Chris S
CS
Canzoniero
Lorella M T
LM
Choi
Dennis W
DW
D000818:Animals; D001692:Biological Transport; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002413:Cations, Divalent / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D004622:Embryo, Mammalian; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D013054:Spectrophotometry, Atomic; D017967:Zinc Compounds / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D015037:Zinc Radioisotopes / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D002712:Chlorides; D017967:Zinc Compounds; D015037:Zinc Radioisotopes; D011189:Potassium Chloride; C016837:zinc chloride