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

Abstract

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.