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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. 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.

SUBMITTER: Hershfinkel M

PROVIDER: S-EPMC2737597 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Intracellular zinc inhibits KCC2 transporter activity.

Hershfinkel Michal M Kandler Karl K Knoch Megan E ME Dagan-Rabin Michal M Aras Mandar A MA Abramovitch-Dahan Chen C Sekler Israel I Aizenman Elias E

Nature neuroscience 20090510 6

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 impo ...[more]

PMID: 19430470

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