Abstracts

Inducible changes in ion channel expression influencing neuronal excitability are emerging as potential mechanisms in human epilepsies. A relative new comer to the list of ion channels involved in epilepsy is the hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN). Several studies in chronic human epilepsy and various animal models of temporal lobe epilepsy (TLE) have reported alterations in the HCN expression and function in the hippocampus. However, these changes have only being reported in immature animals or models with significant neuronal loss or in end stage epileptic patients. Therefore, whether these reported changes in HCN expression are a critical component of epileptogenesis in uncertain., In this study we have measured HCN1 and HCN1 mRNA expression in two different animal models of TLE; the amygdala kindling model (associated with minimal cell loss) and the kainic acid (KA) post-status epilepticus model (associated with significant cell death) during early epileptogenesis. 7-8 week old female rats were studied. The kindled group were electrically stimulated in the left amygdala until [apos]fully kindled[apos] (5 class V seizures according to the racine classification). The KA group received i.p. KA injections (2.5-5mg/kg) hourly until continuous seizures were observed on EEG. At designated time points, brains were extracted and hippocampal subregions (CA1 [amp] CA3) were sectioned. Real time PCR was performed using gene expression assays (Applied Biosystems) and analysis was performed using the [Delta][Delta]C[sub]T[/sub] quantification method., In the [italic]CA1 region of the hippocampus[/italic], HCN1 mRNA expression was significantly reduced in post-KA animals compared to controls. In contrast, HCN1 mRNA expression did not differ between control and kindled animals. There was no difference in HCN2 mRNA expression in either epileptogenic model. In the [italic]CA3 region of the hippocampus,[/italic] HCN1 mRNA expression was significantly reduced in post-KA animals compared to controls. In contrast, HCN1 mRNA expression did not differ between control and kindled animals. There was no difference in HCN2 mRNA expression in either epileptogenic model., A reduction in HCN1 mRNA expression in the CA1 or CA3 region of the hippocampus would alter the balance of HCN1:HCN2 ratio in these neurons and thus the firing properties of these neurons would change. However, since no changes in HCN mRNA expression was observed in the kindled group we question whether the changes we have observed in the post-KA animals is a true epileptogenic response or a non-specific response to cell death post status epilepticus., (Supported by NH[amp]MRC project grant 406640.)