Abstract
We found that K+/Cl− co-transporter 2 (KCC2) activity, monitored with wide-field fluorescence, was inhibited by intracellular Zn2+, a major component of neuronal injury. Zn2+-mediated KCC2 inhibition produced a depolarizing shift of GABAA reversal potentials in rat cortical neurons. Moreover, oxygen-glucose deprivation attenuated KCC2 activity in a Zn2+-dependent manner. The link between Zn2+ and KCC2 activity provides a previously unknown target for neuroprotection and may be important in activity-dependent regulation of inhibitory synaptic transmission.
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Acknowledgements
We thank K. Hartnett and M. Jefferson for expert technical assistance. This work was supported by the US-Israel Binational Science Foundation (grant BSF2007121 to M.H. and E.A.) and the US National Institutes of Health (grants NS043277 to E.A. and DC004199 to K.K.).
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M.H., M.E.K., M.D.-R., M.A.A., C.A.-D. and E.A. performed, analyzed, and designed the experiments. I.S. and K.K. helped with experimental design and analysis. M.H., K.K., I.S. and E.A. wrote and/or edited the paper.
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Hershfinkel, M., Kandler, K., Knoch, M. et al. Intracellular zinc inhibits KCC2 transporter activity. Nat Neurosci 12, 725–727 (2009). https://doi.org/10.1038/nn.2316
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DOI: https://doi.org/10.1038/nn.2316
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