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

Autor: Heinz Beck, Rainer Surges, Tallie Z. Baram, Christiane Rüschenschmidt, Maria Kukley, Johannes Schramm, Amy L. Brewster, Dirk Dietrich
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Patch-Clamp Techniques
Potassium Channels
pharmacology [Pilocarpine]
Hippocampal formation
Biochemistry
Epileptogenesis
Epilepsy
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
physiopathology [Dentate Gyrus]
Cells
Cultured
Neurons
Chemistry
biosynthesis [Potassium Channels]
Pilocarpine
metabolism [Dentate Gyrus]
Anatomy
Hyperpolarization (biology)
physiology [Neurons]
Up-Regulation
metabolism [Neurons]
chemical synthesis [Cyclic Nucleotide-Gated Cation Channels]
medicine.symptom
metabolism [Epilepsy
Temporal Lobe]
medicine.drug
medicine.medical_specialty
therapy [Epilepsy
Temporal Lobe]
physiopathology [Epilepsy
Temporal Lobe]
Biophysics
Cyclic Nucleotide-Gated Cation Channels
Status epilepticus
Article
Internal medicine
ddc:570
medicine
Animals
Humans
Patch clamp
chemical synthesis [Potassium Channels]
Molecular Biology
Dentate gyrus
biosynthesis [Cyclic Nucleotide-Gated Cation Channels]
HCN1 protein
human
Cell Biology
medicine.disease
Rats
Disease Models
Animal
Endocrinology
Epilepsy
Temporal Lobe
Dentate Gyrus
Hcn1 protein
rat
Zdroj: Biochemical and biophysical research communications 420(1), 156-160 (2012). doi:10.1016/j.bbrc.2012.02.133
DOI: 10.1016/j.bbrc.2012.02.133
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: