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Neurobiol Dis. 2000 Aug;7(4):310-20.

Astrocytes are more resistant than neurons to the cytotoxic effects of increased [Zn(2+)](i).

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Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA.


Increased intracellular free Zn(2+) ([Zn(2+)](i)) is toxic to neurons. Glia are more resistant to Zn(2+)-mediated toxicity; however, it is not known if this is because glia are less permeable to Zn(2+) or if glia possess intrinsic mechanisms that serve to buffer or extrude excess [Zn(2+)](i). We used the Zn(2+)-selective ionophore pyrithione to directly increase [Zn(2+)](i) in both neurons and astrocytes. In neurons, a 5-min exposure to 1 microM extracellular Zn(2+) in combination with pyrithione produced widespread toxicity, whereas extensive astrocyte injury was not observed until extracellular Zn(2+) was increased to 10 microM. Measurements with magfura-2 demonstrated that pyrithione increased [Zn(2+)](i) to similar levels in both cell types. We also measured how increased [Zn(2+)](i) affects mitochondrial membrane potential (Deltapsi(m)). In astrocytes, but not in neurons, toxic [Zn(2+)](i) resulted in an acute loss of Deltapsi(m), suggesting that mitochondrial dysregulation may be an early event in [Zn(2+)](i)-induced astrocyte but not neuronal death.

[Indexed for MEDLINE]

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