Audiogenic kindling changes the subunit composition of BK-channels in dentate gyrus of Krushinskii-Molodkina rats

Abstract

Subunit composition of voltage- and Ca2+-sensitive high-conductance K+ channels (BK channels) in dentate gyrus (DG) of Krushinskii-Molodkina (KM) rats, genetically prone to audiogenic seizures, was compared with that of normal Wistar rats, resistant to sound effects. Additionally, long-lasting changes in protein expression of α- and β4-subunits in DG of KM rats after audiogenic kindling (model of temporal lobe epilepsy) was investigated. Western blot analysis revealed no differences between the levels of the pore-forming α-subunit expression in DG of KM and Wistar rats. In contrast, the level of brain-specific auxiliary β4-subunit in DG of KM rats was increased twofold in comparison to that in Wistar rats. It is likely that the observed changes in the BK channel α/β4 subunits ratio can prevent the development of excessive neuronal exitability in DG of KM rats. The results obtained on the model of audiogenic kindling (20 convulsion fits) confirmed this assumption. Thus, α-subunit expression levels in DG of KM rats on day 3 and 14 after the last seizure were increased 2.5 times in comparison with intact KM rats. The expression level of β4 in DG of KM rats 3 days after kindling was reduced to 30% of the control level. On day 14 after finishing audiogenic kindling, a further reduction of β4 protein expression level occurred. We suggest that the changes in the subunit composition of BK channels in DG following chronic seizures can alter functional properties of DG as a physiological filter, which normally prevents the propagation of epileptiform activity in the hippocampus.