G Protein-coupled Inward Rectifier Potassium Channel Subunit 2 In Kainic Acid Induced Expression Changes In The Hippocampus Of Epileptic Rats

Purpose: G protein-coupled inwardly rectifier potassium (GIRK) channel are distributed widely in mammalian central nerve system. In brain, GIRK 1/2 seems to be the predominant heterotetramers which play a pivot role in the regulation of the excitability of neurons and may contribute to the resting potential by leading to a hyperpolarization of membrane potential and reduction of the action potential frequency. In the context, the weaver mouse is the first neurological abnormality directly linked to a genetic point mutation in the GIRK2 protein which includes spontaneous seizure. GIRK2 knock out mice showed normal development but more susceptible than normal mice to seizure induced by GABA antagonist. Here, we first report that the mRNA and protein expression of GIRK subunit 2 is altered in kainic acid-induced epileptic rat hippocampus.Method: 1. Rats were injected with kainate acid 14mg/kg intraperitoneally to establish an acute and chronic temporal lobe epilepsy model. The controls were injected with saline instead of kainate. At 3. 6^ 12, 24. 48 hours and 7^ 30 days after kainate injection, the rats were anaesthetized and perfused.2. By use of in situ hybridization, the GIRK2 mRNA were analyzed at different time quantitatively in the dentate gyrus^ CA1, CA3 regions ofhippocampus.3. GIRK2 protein in the various subfields of hippocampus were detected by immunocytochemistry at the same time points as set in situ hybridization. The results were analyzed quantitatively by image analytical system.Results: 1. The succeed rate on establishment kainate-induced temporal lobe epilepsy was 80%, accordant to previous reports. During different period, rats manifested SE and spontaneous recurrent seizures.2. The expression of GIRK2 mRNA and proteins could be observed in all regions of hippocampus in both groups of rats.3. KA induced seizures caused a significant increase in GIRK2 messenger RNA abundance at 12, 24h and 30 days time point.4. An only significant increase in GIRK2 immunoreactivity was in the DG area at 30 days time point.Conclusion: GIRK2 is abundantly expressed in rat hippocampus and has an anatomically specific expression. Change in mRNA and protein expression of GIRK2 in epileptic rat hippocampus is up-regulated, which may be an adaptive response to over-excitability of neuron networks and prevent the over-excitability spread in hippocampus (DGæ¡ŸA3æ¡ŸA1).