Retraction. Clc-2 knockout attenuated experimental temporal lobe epilepsy in mice by tonic inhibition mediated by GABAA receptors

Temporal lobe epilepsy (TLE), the most prevalent form of epilepsy, is often associated with drug-resistant seizures. In TLE, altered function of γ-aminobutyric acid (GABA)A receptors (GABAARs) results in potentiation of excitatory and/or failure of inhibitory neurotransmission, which contributes to seizure induction and propagation. Our previous study suggested that chloride channel-2 (Clc-2) contributed to chronically elevated tonic inhibition mediated by GABAARs in a rat model of TLE. In the present study, we used Clc-2 knockout mice to investigate further the role of Clc-2 and its interaction with tonic GABAergic inhibition in a model of TLE. The results revealed that knockout of Clc-2 decreased tonic seizure protection, latency of clonic seizure, seizure threshold and mortality protection in mice. Clc-2 knockout decreased the action potential (AP)peak and APthreshold, Clc-2 currents and GABAAR-mediated tonic inhibition in CA1 pyramidal neurons. Thus, the voltage-gated chloride channel Clc-2, which was functionally upregulated in CA1 pyramidal cells after seizures, may provide protection against TLE by its regulation of action potentials, Clc-2 currents and GABAARs in the CA1 region of the hippocampus.