Objective To study the alternation in the expression of G protein-gated inwardly rectifying potassium (GIRK) channels on the cell membrane of hippocampal neurons at different periods after pilocarpine induced seizures, and to explore its possible regulatory mechanisms.
Methods Adult male SD rats were randomly divided into a control group and a pilocarpine model group. Pilocarpine was used to induce status epilepticus (SE). The hippocampal tissus were taken to extract membrane proteins in the acute phase (24 h) and the chronic phase (30 d) after SE. The expression changes of hippocampal membrane protein GIRK channel subunit proteins GIRK1 and GIRK2 were detected by Western Blot, and the expression of p-Akt and Akt proteins in the whole hippocampus was also detected at the same time. The cell epilepsy model was used to observe the changes of Kir currents in hippocampal neurons after the addition of PI3K inhibitor wortmannin and LY294002.
Results The expression of GIRK1 and GIRK2 protein on the rat neuronal membrane was significantly down-regulated compared with the control group in the acute phase after the SE induced by pilocarpine (P < 0.05). The expression of GIRK1 in the hippocampal membrane protein of rats decreased in the chronic phase after the onset of SE (P < 0.05), while the expression of GIRK2 protein did not change significantly. The ratio of p-Akt (308) and Akt protein expression levels increased significantly in the acute phase after the seizure induced by pilocarpine in rats compared with the control group (P < 0.05), but did not change in the chronic phase after the seizure of SE. In the cellular epilepsy model, wortmannin and LY294002 had no significant effect on the Kir current of epileptiform neurons.
Conclusions In the acute phase after seizures of SE induced by pilocarpine in rats and mice, the expression of GIRK channel protein in the hippocampus is down-regulated to varying degrees, and the PI3K/Akt pathway is significantly activated during the same period.
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