title: ClC-2 contributes to tonic inhibition mediated by α5 subunit-containing GABA(A) receptor in experimental temporal lobe epilepsy.
abstract: Temporal lobe epilepsy (TLE), characterized by spontaneous recurrent seizures, learning and memory impairments is associated with neurodegeneration, abnormal reorganization of the circuitry and loss of functional inhibition in hippocampus. In adult hippocampus, the GABAergic cells mediate the major inhibitory function of the principal neurons, promoting the Cl(-) entry through the GABA(A) receptor, whether through phasic (synaptic) or tonic (extrasynaptic) conductance. Aside from classical synaptic component, tonic GABAergic inhibition mediated by extrasynaptic GABA(A) receptor received increasing attention over the past years. There is growing evidence that tonic inhibition plays an important role in epilepsy, memory and cognition. Since GABA(A) receptor-mediated inhibition depends on the maintenance of intracellular Cl(-) concentration at low levels in mature neurons, a shift in E(cl) is likely to participate in the generation and not merely a consequence of TLE. As we know, chloride channel-2 (ClC-2) is a member of the supergene family of voltage-gated chloride channels, it constitutes part of the background conductance and is involved in chloride extrusion. Here we show that ClC-2 were upregulated functionally in CA1 pyramidal cells in pilocarpine-treated rats, and that an observed increase in ClC-2 currents in CA1 pyramidal cells was reversed by L655,708, a specific antagonist of α5 subunit-containing GABA(A) receptor.
authors.affiliation: Department of Neurology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Y-X
authors.initials: YX
authors.lastname: Ge
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: H-Y
authors.initials: HY
authors.lastname: Tang
authors.forename: X-G
authors.initials: XG
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000503:physiopathology; D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels / Q000502:physiology*; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; C000715429:Clcn2 protein, rat; C511535:Gabra5 protein, rat; D011963:Receptors, GABA-A