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Tarek Z. Deeb, Yasuko Nakamura, Greg D. Frost, Paul A. Davies and Stephen J. Moss Disrupted Cl− homeostasis contributes to reductions in the inhibitory efficacy of diazepam during hyperexcited states European Journal of Neuroscience 38

Version of Record online: 29 APR 2013 | DOI: 10.1111/ejn.12241

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Several commonly used therapeutic drugs target Cl permeable GABAA receptors. In the current study, hyperexcitability caused by glutamate or by inhibition of KCC2 rapidly increased Cl levels inside neurons. This buildup reduced the ability of diazepam to suppress neuronal activity. However, the same conditions did not affect inhibition by propofol. Changes in intracellular Cl could therefore selectively impact the therapeutic efficacy of GABAA modulators during specific pathological states.

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