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Hyperpolarization-activated cation current Iₕ of dentate gyrus granule cells is upregulated in human and rat temporal lobe epilepsy

Surges, Rainer, Kukley, Maria, Brewster, Amy, Rüschenschmidt, Christiane, Schramm, Johannes, Baram, Tallie Z., Beck, Heinz, Dietrich, Dirk
Biochemical and biophysical research communications 2012 v.420 no.1 pp. 156-160
epilepsy, gene expression, humans, in situ hybridization, messenger RNA, models, patch-clamp technique, patients, pilocarpine, rats, sclerosis, seizures
The hyperpolarization-activated cation current Iₕ is an important regulator of neuronal excitability and may contribute to the properties of the dentate gyrus granule (DGG) cells, which constitute the input site of the canonical hippocampal circuit. Here, we investigated changes in Iₕ in DGG cells in human temporal lobe epilepsy (TLE) and the rat pilocarpine model of TLE using the patch-clamp technique. Messenger-RNA (mRNA) expression of Iₕ-conducting HCN1, 2 and 4 isoforms was determined using semi-quantitative in-situ hybridization. Iₕ density was ∼1.8-fold greater in DGG cells of TLE patients with Ammon’s horn sclerosis (AHS) as compared to patients without AHS. The magnitude of somatodendritic Iₕ was enhanced also in DGG cells in epileptic rats, most robustly during the latent phase after status epilepticus and prior to the occurrence of spontaneous epileptic seizures. During the chronic phase, Iₕ was increased ∼1.7-fold. This increase of Iₕ was paralleled by an increase in HCN1 and HCN4 mRNA expression, whereas HCN2 expression was unchanged. Our data demonstrate an epilepsy-associated upregulation of Iₕ likely due to increased HCN1 and HCN4 expression, which indicate plasticity of Iₕ during epileptogenesis and which may contribute to a compensatory decrease in neuronal excitability of DGG cells.