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Intracellular zinc inhibits KCC2 transporter activity

Nature Neuroscience volume 12, pages 725–727 (2009)Cite this article

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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Figure 1: Increase in [Zn2+]i inhibits KCC2 activity.
Figure 2: Effects of [Zn2+]i on EGABA and KCC2 inhibition by OGD in neurons.

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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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Author notes

  1. Megan E Knoch

    Present address: Present address: Biology Department, Indiana University of Pennsylvania, Indiana, Pennsylvania, USA.,

Authors and Affiliations

  1. Department of Morphology Ben Gurion University, Beer-Sheva, Israel

    Michal Hershfinkel, Michal Dagan-Rabin & Chen Abramovitch-Dahan

  2. Zlotowski Center for Neuroscience, Ben Gurion University, Beer-Sheva, Israel

    Michal Hershfinkel, Michal Dagan-Rabin, Chen Abramovitch-Dahan & Israel Sekler

  3. Departments of Neurobiology University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Karl Kandler, Megan E Knoch, Mandar A Aras & Elias Aizenman

  4. Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Karl Kandler

  5. Department of Physiology, Ben Gurion University, Beer-Sheva, Israel

    Israel Sekler

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  1. Michal Hershfinkel
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  2. Karl Kandler
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Contributions

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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Correspondence to Michal Hershfinkel.

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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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