ArticleThe Journal of physiology2006
Functional stabilization of weakened thalamic pacemaker channel regulation in rat absence epilepsy.
Article in The Journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- Genetic Animal Models of Idiopathic Generalized Epilepsies: What Can We Learn from Them?Biomedicines · 2025Review
- Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations.Aging and disease · 2024Review
- Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy.International journal of molecular sciences · 2023Review
- Article
- Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures.JCI insight · 2019Article
- Suppression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function in Thalamocortical Neurons Prevents Genetically Determined and Pharmacologically Induced Absence Seizures.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Modulation of Hyperpolarization-Activated Inward Current and Thalamic Activity Modes by Different Cyclic Nucleotides.Frontiers in cellular neuroscience · 2018Article
- Robotic navigation to subcortical neural tissue for intracellular electrophysiology in vivo.Journal of neurophysiology · 2017Article
- Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels in Epilepsy.Cold Spring Harbor perspectives in medicine · 2016Review
- Prenatal Valproate Exposure Differentially Affects Parvalbumin-Expressing Neurons and Related Circuits in the Cortex and Striatum of Mice.Frontiers in molecular neuroscience · 2016Article
- Thalamocortical neurons display suppressed burst-firing due to an enhanced Ih current in a genetic model of absence epilepsy.Pflugers Archiv : European journal of physiology · 2015Article
- An N-terminal deletion variant of HCN1 in the epileptic WAG/Rij strain modulates HCN current densities.Frontiers in molecular neuroscience · 2015Article
- Regulating excitability of peripheral afferents: emerging ion channel targets.Nature neuroscience · 2014Review
- Pathogenesis of epilepsy: challenges in animal models.Iranian journal of basic medical sciences · 2013Review
- HCN and KV7 (M-) channels as targets for epilepsy treatment.Neuropharmacology · 2013Review
- Ca(2+)-dependent large conductance K(+) currents in thalamocortical relay neurons of different rat strains.Pflugers Archiv : European journal of physiology · 2013Article
- Novel HCN2 mutation contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner.PloS one · 2013Article
- Neurochemical and behavioral features in genetic absence epilepsy and in acutely induced absence seizures.ISRN neurology · 2013Article
- Adenylyl cyclases: expression in the developing rat thalamus and their role in absence epilepsy.Journal of molecular neuroscience : MN · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Aberrant function of pacemaker currents (Ih), carried by hyperpolarization-activated cation non-selective (HCN) channels, affects neuronal excitability and accompanies epilepsy, but its distinct roles in epileptogenesis and chronic epilepsy are unclear. We probed Ih function and subunit composition during both pre- and chronically epileptic stages in thalamocortical (TC) neurones of the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). Voltage gating of Ih was unaltered in mature somatosensory TC cells, both in vivo and in vitro. However, the enhancement of Ih by phasic, near-physiological, cAMP pulses was diminished by approximately 40% and the half-maximal cAMP concentration increased by approximately 5-fold. This decreased responsiveness of Ih to its major cellular modulator preceded epilepsy onset in GAERS, persisted throughout the chronic state, and was accompanied by an enhanced expression of the cAMP-insensitive HCN1 channel mRNA (> 50%), without changes in the mRNA levels of HCN2 and HCN4. To assess for alterations in TC cell excitability, we monitored the slow up-regulation of Ih that is induced by Ca2+-triggered cAMP synthesis and important for terminating in vitro synchronized oscillations. Remarkably, repetitive rebound Ca2+ spikes evoked normal slow Ih up-regulation in mature GAERS neurones; that sufficed to attenuate spontaneous rhythmic burst discharges. These adaptive mechanisms occurred upstream of cAMP turnover and involved enhanced intracellular Ca2+ accumulation upon repetitive low-threshold Ca2+ discharges. Therefore, HCN channels appear to play a dual role in epilepsy. Weakened cAMP binding to HCN channels precedes, and likely promotes, epileptogenesis in GAERS, whereas compensatory mechanisms stabilizing Ih function contribute to the termination of spike-and-wave discharges in chronic epilepsy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.