Expression of GABA-A Receptors and Cation-Chloride Cotransporters in the Hippocampus of Krushinsky–Molodkina Audiogenic Rats during the Postnatal Development

Epilepsy development can be caused by impaired postsynapticaction of GABA that is mediated by altered expression of GABA-Areceptors and cation-chloride cotransporters, KCC2 (K⁺/Cl^– cotransporter2) and NKCC1 (Na⁺/K⁺/Cl^– cotransporter1). In the present study, we analyzed the expression of GABA-A receptors,KCC2, and NKCC1 in the hippocampus of Krushinsky–Molodkina (KM)rats, genetically prone to audiogenic seizures (AGS), during thefirst few months of the postnatal development (at P15, P60, andP120). Wistar rats of the corresponding ages were used as the control groups.In the hippocampus of KM pups, we observed downregulation of bothKCC2 and NKCC1; however, the expression of GABA-A receptor α1-subunit(GABAAR(α1)) was increased. Moreover, KCC2 was not detected in anabnormally broad region of the granular layer, indicating the Cl^– imbalanceand impaired GABA-mediated inhibition in postsynaptic targets ofGABA. These results suggested a delayed maturation of the hippocampalGABAergic system in KM rats in comparison with Wistar rats. In adultKM rats (P120) with fully developed susceptibility to AGS, normalizationof both KCC2 and NKCC1 expression and KCC2 phosphorylation in thehippocampus was revealed. In contrast, GABAAR(α1) expression wasdecreased. We supposed that lower expression of GABA-A receptorsin the hippocampus of adult KM rats might contribute either to theestablishment of increased convulsive readiness or to hyperexcitationof the hippocampus during audiogenic kindling.