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Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival
Author(s) -
Pellegrino Christophe,
Gubkina Olena,
Schaefer Michael,
Becq Hélène,
Ludwig Anastasia,
Mukhtarov Marat,
Chudotvorova Ilona,
Corby Severine,
Salyha Yuriy,
Salozhin Sergey,
Bregestovski Piotr,
Medina Igor
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.203703
Subject(s) - excitotoxicity , intracellular , hippocampal formation , microbiology and biotechnology , excitatory postsynaptic potential , premovement neuronal activity , neuroprotection , inhibitory postsynaptic potential , chemistry , nmda receptor , homeostasis , gabaa receptor , glutamate receptor , biology , neuroscience , receptor , biochemistry
Non‐technical summary ‘To be, or not to be’– thousands of neurons are facing this Shakespearean question in the brains of patients suffering from epilepsy or the consequences of a brain traumatism or stroke. The destiny of neurons in damaged brain depends on tiny equilibrium between pro‐survival and pro‐death signalling. Numerous studies have shown that the activity of the neuronal potassium chloride co‐transporter KCC2 strongly decreases during a pathology. However, it remained unclear whether the change of the KCC2 function protects neurons or contributes to neuronal death. Here, using cultures of hippocampal neurons, we show that experimental silencing of endogenous KCC2 using an RNA interference approach or a dominant negative mutant reduces neuronal resistance to toxic insults. In contrast, the artificial gain of KCC2 function in the same neurons protects them from death. This finding highlights KCC2 as a molecule that plays a critical role in the destiny of neurons under toxic conditions and opens new avenues for the development of neuroprotective therapy.