ArticleThe Journal of general physiology2004
S4 movement in a mammalian HCN channel.
Article in The Journal of general physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 95 citations in OpenAlex.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- PIP2-driven cytoplasmic domain motions are coupled to Kir2 channel gating.The Journal of general physiology · 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
- Domain coupling in allosteric regulation of SthK measured using time-resolved transition metal ion FRET.eLife · 2025Article
- An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels.bioRxiv : the preprint server for biology · 2025Article
- Article
- 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
- Uncoupling of Voltage- and Ligand-Induced Activation in HCN2 Channels by Glycine Inserts.Frontiers in physiology · 2022Article
- A second S4 movement opens hyperpolarization-activated HCN channels.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Electromechanical coupling mechanism for activation and inactivation of an HCN channel.Nature communications · 2021Article
- Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating.eLife · 2019Article
- Article
- The HCN channel voltage sensor undergoes a large downward motion during hyperpolarization.Nature structural & molecular biology · 2019Article
- Characterization of drug binding within the HCN1 channel pore.Scientific reports · 2019Article
- New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question.International journal of molecular sciences · 2019Review
- Bipolar switching by HCN voltage sensor underlies hyperpolarization activation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Insights into the molecular mechanism for hyperpolarization-dependent activation of HCN channels.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Mechanical transduction of cytoplasmic-to-transmembrane-domain movements in a hyperpolarization-activated cyclic nucleotide-gated cation channel.The Journal of biological chemistry · 2018Article
- Structural insights into the mechanisms of CNBD channel function.The Journal of general physiology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hyperpolarization-activated, cyclic nucleotide-gated ion channels (HCN) mediate an inward cation current that contributes to spontaneous rhythmic firing activity in the heart and the brain. HCN channels share sequence homology with depolarization-activated Kv channels, including six transmembrane domains and a positively charged S4 segment. S4 has been shown to function as the voltage sensor and to undergo a voltage-dependent movement in the Shaker K+ channel (a Kv channel) and in the spHCN channel (an HCN channel from sea urchin). However, it is still unknown whether S4 undergoes a similar movement in mammalian HCN channels. In this study, we used cysteine accessibility to determine whether there is voltage-dependent S4 movement in a mammalian HCN1 channel. Six cysteine mutations (R247C, T249C, I251C, S253C, L254C, and S261C) were used to assess S4 movement of the heterologously expressed HCN1 channel in Xenopus oocytes. We found a state-dependent accessibility for four S4 residues: T249C and S253C from the extracellular solution, and L254C and S261C from the internal solution. We conclude that S4 moves in a voltage-dependent manner in HCN1 channels, similar to its movement in the spHCN channel. This S4 movement suggests that the role of S4 as a voltage sensor is conserved in HCN channels. In addition, to determine the reason for the different cAMP modulation and the different voltage range of activation in spHCN channels compared with HCN1 channels, we constructed a COOH-terminal-deleted spHCN. This channel appeared to be similar to a COOH-terminal-deleted HCN1 channel, suggesting that the main functional differences between spHCN and HCN1 channels are due to differences in their COOH termini or in the interaction between the COOH terminus and the rest of the channel protein in spHCN channels compared with HCN1 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.