ArticleeLife2019
The HCN domain couples voltage gating and cAMP response in hyperpolarization-activated cyclic nucleotide-gated channels.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 95 citations in OpenAlex.
- Semaglutide drives weight loss through cAMP-dependent mechanisms in GLP1R-expressing hindbrain neurons.Nature metabolism · 2026Article
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- The proximal N-terminus of IRAG is required for potentiation of HCN4 channels.bioRxiv : the preprint server for biology · 2026Article
- Structural determinants of voltage sensitivity in hyperpolarization-activated ion channels and their persistence in the evolutionary scale.Pflugers Archiv : European journal of physiology · 2026Article
- Predicting Binding Affinities for the Binding Domain of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Isoforms Using Free-Energy Perturbation.bioRxiv : the preprint server for biology · 2026Article
- An inter-subunit path is required for entropically-driven and negatively cooperative binding of cyclic nucleotides in the HCN2 channel.Communications biology · 2026Article
- Towards a unified gating scheme for the CNBD ion channel family.The Journal of general physiology · 2026Review
- Extracellular activation of HCN4 by a subtype-specific nanobody.Nature communications · 2025Article
- Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Insights into ion channels to identify drug target for neuropathic pain management.Inflammopharmacology · 2025Review
- Hippocampal dorsal CA1: Functional connectivity and role in HCN channelopathies in affective diseases and epilepsy.IBRO neuroscience reports · 2025Article
- AtKC1 inhibits AKT1 activation via its amino-terminal inhibitory domain.Plant communications · 2025Article
- Molecular insights into the rescue mechanism of an HERG activator against severe LQT2 mutations.Journal of biomedical science · 2025Article
- A Novel Loss of Function Variant inMolecular syndromology · 2025Article
- GORK KNature communications · 2025Article
- Hyperpolarization-activated cyclic nucleotide-gated channels and epilepsy: genetics, circuits, and treatments.Frontiers in neurology · 2025Review
- Analysis of epilepsy-associated variants in HCN3 - Functional implications and clinical observations.Epilepsia open · 2024Article
- Mapping the contribution of the C-linker domain to gating polarity in CNBD channels.Biophysical journal · 2024Article
- Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.Journal of chemical information and modeling · 2024Article
- Cannabidiol potentiates hyperpolarization-activated cyclic nucleotide-gated (HCN4) channels.The Journal of general physiology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control spontaneous electrical activity in heart and brain. Binding of cAMP to the cyclic nucleotide-binding domain (CNBD) facilitates channel opening by relieving a tonic inhibition exerted by the CNBD. Despite high resolution structures of the HCN1 channel in the cAMP bound and unbound states, the structural mechanism coupling ligand binding to channel gating is unknown. Here we show that the recently identified helical HCN-domain (HCND) mechanically couples the CNBD and channel voltage sensing domain (VSD), possibly acting as a sliding crank that converts the planar rotational movement of the CNBD into a rotational upward displacement of the VSD. This mode of operation and its impact on channel gating are confirmed by computational and experimental data showing that disruption of critical contacts between the three domains affects cAMP- and voltage-dependent gating in three HCN isoforms.
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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.