Intracellular zinc inhibits KCC2 transporter activity

Michal Hershfinkel; Karl Kandler; Megan E. Knoch; Michal Dagan-Rabin; Mandar A. Aras; Chen Abramovitch-Dahan; Israel Sekler; Elias Aizenman

doi:10.1038/nn.2316

Intracellular zinc inhibits KCC2 transporter activity

Michal Hershfinkel, Karl Kandler, Megan E. Knoch, Michal Dagan-Rabin, Mandar A. Aras, Chen Abramovitch-Dahan, Israel Sekler, Elias Aizenman

Physiology and Cell Biology

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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. Zn²⁺- 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 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.

Original language	English
Pages (from-to)	725-727
Number of pages	3
Journal	Nature Neuroscience
Volume	12
Issue number	6
DOIs	https://doi.org/10.1038/nn.2316
State	Published - 1 Jun 2009

ASJC Scopus subject areas

Neuroscience (all)

Access to Document

10.1038/nn.2316

Cite this

@article{be68010e48924fe6a515ff8e08047c77,

title = "Intracellular zinc inhibits KCC2 transporter activity",

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. Zn2+- 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 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.",

author = "Michal Hershfinkel and Karl Kandler and Knoch, {Megan E.} and Michal Dagan-Rabin and Aras, {Mandar A.} and Chen Abramovitch-Dahan and Israel Sekler and Elias Aizenman",

year = "2009",

month = jun,

day = "1",

doi = "10.1038/nn.2316",

language = "English",

volume = "12",

pages = "725--727",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Intracellular zinc inhibits KCC2 transporter activity

AU - Hershfinkel, Michal

AU - Kandler, Karl

AU - Knoch, Megan E.

AU - Dagan-Rabin, Michal

AU - Aras, Mandar A.

AU - Abramovitch-Dahan, Chen

AU - Sekler, Israel

AU - Aizenman, Elias

PY - 2009/6/1

Y1 - 2009/6/1

N2 - 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. Zn2+- 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 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.

AB - 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. Zn2+- 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 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.

UR - http://www.scopus.com/inward/record.url?scp=67349107091&partnerID=8YFLogxK

U2 - 10.1038/nn.2316

DO - 10.1038/nn.2316

M3 - Article

AN - SCOPUS:67349107091

SN - 1097-6256

VL - 12

SP - 725

EP - 727

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 6

ER -

Intracellular zinc inhibits KCC2 transporter activity

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this