Elevated voltage gated Cl− channel expression enhances fast paired-pulse inhibition in the dentate gyrus of seizure sensitive gerbil

The present study was performed to determine whether the voltage gated Cl− channel (CLC) expression is altered in the hippocampus of seizure sensitive (SS) gerbils, and to identify the strong fast paired-pulse inhibition in the dentate gyrus of SS gerbils is associated with altered CLC expression. In the hippocampal proper and the granule cell layer of the dentate gyrus of the SS gerbils, strong CLC-2 immunoreactivity was detected, as compared with seizure resistant (SR) gerbils. In addition, CLC-3 immunoreactivity was observed in the CA1-3 pyramidal cells, and the granule cell and the molecular layer of the dentate gyrus in the SS gerbils, whereas its immunoreactivity was rarely detected in the SR gerbils. However, CLC-3 immunoreactivity in the mossy fiber was reduced, as compared with SR gerbils. Moreover, infusion of the potential CLC inhibitor (4,4′-diisothiocyanostibene-2,2′-disulfanic acid, DIDS) reduced fast paired-pulse inhibition in the dentate gyrus of SS gerbils, although evoked responses in the dentate gyrus between SR and SS gerbils were similarly detected. These findings suggest that enhancement of CLC expression in the dentate gyrus of SS gerbils may be one of the compensatory responses for reduced GABAA receptor-mediated fast postsynaptic inhibitory potentials.