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The Journal of Neuroscience, 1999, 19:RC31:1-6

RAPID COMMUNICATION
Measurement of Intracellular Free Zinc Concentrations Accompanying Zinc-Induced Neuronal Death

Lorella M. T. Canzoniero, Dorothy M. Turetsky, and Dennis W. Choi

Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110

Toxic zinc influx may contribute to selective neuronal death after transient global ischemia. We previously used the high-affinity (K_D = 27 nM) fluorescent dye mag-fura-5 to detect initial increases in neuronal intracellular free Zn²⁺ ([Zn²⁺]_i) associated with brief Zn²⁺ exposure. Here we used the specific low-affinity Zn²⁺ indicator Newport Green (K_D = 1 µM) to measure the peak levels of [Zn²⁺]_i attained during prolonged, toxic exposures to extracellular Zn²⁺. Murine cortical cell cultures exposed for 5-10 min to 300 µM Zn²⁺ in the presence of kainate or elevated extracellular K⁺ developed widespread neuronal death over the next 24 hr. Such Zn²⁺ exposure under depolarizing conditions was accompanied by a large increase in [Zn²⁺]_i reaching several hundred nanomolar, which gradually recovered over the next 20-40 min after termination of Zn²⁺ exposure. Both the level of [Zn²⁺]_i elevation and the extent of subsequent neuronal death depended on the concentration of extracellular Zn²⁺ between 30 µM and 1 mM. In contrast, exposure to 300 µM Zn²⁺ in the presence of 300 µM NMDA resulted in little increase in [Zn²⁺]_i and little neuronal death, suggesting that NMDA receptor-gated channels are less important as a route of toxic Zn²⁺ entry than voltage-gated calcium channels.

Key words: voltage-gated calcium channels; calcium; depolarization; kainate; NMDA; neurotoxicity

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Copyright © 0000 Society for Neuroscience  0270-6474/0/$05.00/0

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