Abstract
We found that K(+)/Cl(-) co-transporter 2 (KCC2) activity, monitored with wide-field fluorescence, was inhibited by intracellular Zn(2+), a major component of neuronal injury. Zn(2+)-mediated KCC2 inhibition produced a depolarizing shift of GABA(A) reversal potentials in rat cortical neurons. Moreover, oxygen-glucose deprivation attenuated KCC2 activity in a Zn(2+)-dependent manner. The link between Zn(2+) and KCC2 activity provides a previously unknown target for neuroprotection and may be important in activity-dependent regulation of inhibitory synaptic transmission.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cerebral Cortex / metabolism*
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Cerebral Cortex / physiopathology
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Chlorides / metabolism
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Cytoprotection / drug effects
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Cytoprotection / physiology
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Humans
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Hypoxia-Ischemia, Brain / metabolism*
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Hypoxia-Ischemia, Brain / physiopathology
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Intracellular Fluid / metabolism
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K Cl- Cotransporters
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Microscopy, Fluorescence
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Nerve Degeneration / etiology
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Nerve Degeneration / metabolism*
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Nerve Degeneration / physiopathology
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Neural Inhibition / drug effects
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Neural Inhibition / physiology
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Neurons / metabolism*
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Organ Culture Techniques
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Potassium / metabolism
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Rats
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Symporters / drug effects
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Symporters / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Zinc / metabolism*
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Zinc / pharmacology
Substances
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Chlorides
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Symporters
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Zinc
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Potassium