ArticleNature communications2024
Structural basis for hyperpolarization-dependent opening of human HCN1 channel.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Acute pretrauma ethanol exacerbates PTSD-like phenotype in rats and is reversed by early intranasal ketamine.Scientific reports · 2026Article
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- Selectivity Filter Dynamics Define Ion Conductance and Selectivity Differences in CNG and HCN Channels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural and functional characterization of Caenorhabditis elegans cyclic GMP-activated channel TAX-4 via molecular dynamics simulations.European biophysics journal : EBJ · 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
- Towards a unified gating scheme for the CNBD ion channel family.The Journal of general physiology · 2026Review
- Article
- Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.Cell research · 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
- Atomistic mechanism of non-selective cation permeation in cyclic nucleotide-gated CNGA1 ion channel by molecular dynamics simulations.Communications biology · 2025Article
- Voltage sensor conformations induced by LQTS-associated mutations in hERG potassium channels.Nature communications · 2025Article
- Insights into ion channels to identify drug target for neuropathic pain management.Inflammopharmacology · 2025Review
- An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels.bioRxiv : the preprint server for biology · 2025Article
- Structural basis of human NaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- GORK KNature communications · 2025Article
- Subunit-specific conductance of single homomeric and heteromeric HCN pacemaker channels at femtosiemens resolution.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.Science advances · 2025Article
- Worldwide Sodium Channel Conference, January 31st-February 2nd, 2024, Grindelwald, Switzerland.Bioelectricity · 2024Article
- Membrane lipid nanodomains modulate HCN pacemaker channels in nociceptor DRG neurons.Nature communications · 2024Article
- Different fluorescent labels report distinct components of spHCN channel voltage sensor movement.The Journal of general physiology · 2024Article
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Abstract
Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN and related plant ion channels activate upon membrane hyperpolarization. Although functional studies have identified residues in the interface between the voltage-sensing and pore domain as crucial for inverted electromechanical coupling, the structural mechanisms for this unusual voltage-dependence remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 corresponding to Closed, Open, and a putative Intermediate state. Our structures reveal that the downward motion of the gating charges past the charge transfer center is accompanied by concomitant unwinding of the inner end of the S4 and S5 helices, disrupting the tight gating interface observed in the Closed state structure. This helix-coil transition at the intracellular gating interface accompanies a concerted iris-like dilation of the pore helices and underlies the reversed voltage dependence of HCN channels.
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