Intracellular zinc inhibits KCC2 transporter activity.
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.
Hershfinkel
Michal
M
Department of Morphology, Ben Gurion University, Beer-Sheva, Israel. hmichal@bgu.ac.il
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
D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D002712:Chlorides / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D007424:Intracellular Fluid / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D027981:Symporters / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology; D000096922:K Cl- Cotransporters
D002712:Chlorides; D011188:Potassium; D027981:Symporters; D015032:Zinc; D000096922:K Cl- Cotransporters