title: Hyperpolarization-activated cation current Ih of dentate gyrus granule cells is upregulated in human and rat temporal lobe epilepsy.
abstract: The hyperpolarization-activated cation current I(h) 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 I(h) 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 I(h)-conducting HCN1, 2 and 4 isoforms was determined using semi-quantitative in-situ hybridization. I(h) 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 I(h) 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, I(h) was increased ∼1.7-fold. This increase of I(h) was paralleled by an increase in HCN1 and HCN4 mRNA expression, whereas HCN2 expression was unchanged. Our data demonstrate an epilepsy-associated upregulation of I(h) likely due to increased HCN1 and HCN4 expression, which indicate plasticity of I(h) during epileptogenesis and which may contribute to a compensatory decrease in neuronal excitability of DGG cells.
authors.affiliation: Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. rainer.surges@googlemail.com
authors.forename: Rainer
authors.initials: R
authors.lastname: Surges
authors.forename: Maria
authors.initials: M
authors.lastname: Kukley
authors.forename: Amy
authors.initials: A
authors.lastname: Brewster
authors.forename: Christiane
authors.initials: C
authors.lastname: Rüschenschmidt
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.forename: Tallie Z
authors.initials: TZ
authors.lastname: Baram
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: Dirk
authors.initials: D
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000096:biosynthesis* / Q000138:chemical synthesis; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000494:pharmacology; D015221:Potassium Channels / Q000096:biosynthesis* / Q000138:chemical synthesis; D051381:Rats; D015854:Up-Regulation
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578665:HCN1 protein, human; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D010862:Pilocarpine