ArticleNature structural & molecular biology2019
The HCN channel voltage sensor undergoes a large downward motion during hyperpolarization.
Article in Nature structural & molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 75 citations in OpenAlex.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- Structural determinants of voltage sensitivity in hyperpolarization-activated ion channels and their persistence in the evolutionary scale.Pflugers Archiv : European journal of physiology · 2026Article
- Real-time imaging of protein microenvironment changes in cells with rotor-based fluorescent amino acids.Nature chemical biology · 2026Article
- Voltage sensor conformations induced by LQTS-associated mutations in hERG potassium channels.Nature communications · 2025Article
- An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels.bioRxiv : the preprint server for biology · 2025Article
- Fluorescent non-canonical amino acid provides insight into the human serotonin transporter.Nature communications · 2024Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Different fluorescent labels report distinct components of spHCN channel voltage sensor movement.The Journal of general physiology · 2024Article
- Article
- Structural basis for hyperpolarization-dependent opening of human HCN1 channel.Nature communications · 2024Article
- Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism.International journal of molecular sciences · 2024Article
- Article
- Direct regulation of the voltage sensor of HCN channels by membrane lipid compartmentalization.Nature communications · 2023Article
- Structural Basis for Hyperpolarization-dependent Opening of the Human HCN1 Channel.bioRxiv : the preprint server for biology · 2023Article
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Interplay between VSD, pore, and membrane lipids in electromechanical coupling in HCN channels.eLife · 2023Article
- Similar voltage-sensor movement in spHCN channels can cause closing, opening, or inactivation.The Journal of general physiology · 2023Article
- Structural basis for severe pain caused by mutations in the S4-S5 linkers of voltage-gated sodium channel NaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- The voltage-sensing domain of a hERG1 mutant is a cation-selective channel.Biophysical journal · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Voltage-gated ion channels (VGICs) contain positively charged residues within the S4 helix of the voltage-sensing domain (VSD) that are displaced in response to changes in transmembrane voltage, promoting conformational changes that open the pore. Pacemaker hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are unique among VGICs because their open probability is increased by membrane hyperpolarization rather than depolarization. Here we measured the precise movement of the S4 helix of a sea urchin HCN channel using transition metal ion fluorescence resonance energy transfer (tmFRET). We show that the S4 undergoes a substantial (~10 Å) downward movement in response to membrane hyperpolarization. Furthermore, by applying distance constraints determined from tmFRET experiments to Rosetta modeling, we reveal that the carboxy-terminal part of the S4 helix exhibits an unexpected tilting motion during hyperpolarization activation. These data provide a long-sought glimpse of the hyperpolarized state of a functioning VSD and also a framework for understanding the dynamics of reverse gating in HCN channels.
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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.