ArticleThe Journal of general physiology2007
Kinetic relationship between the voltage sensor and the activation gate in spHCN channels.
Article in The Journal of general physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- HCN1 is a primary HCN Pacemaker Channel in Neurons.Nature communications · 2026Article
- 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
- Different fluorescent labels report distinct components of spHCN channel voltage sensor movement.The Journal of general physiology · 2024Article
- Article
- Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism.International journal of molecular sciences · 2024Article
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- Article
- A second S4 movement opens hyperpolarization-activated HCN channels.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Modulation of KFrontiers in pharmacology · 2020Article
- Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating.eLife · 2019Article
- The contribution of voltage clamp fluorometry to the understanding of channel and transporter mechanisms.The Journal of general physiology · 2019Review
- The HCN channel voltage sensor undergoes a large downward motion during hyperpolarization.Nature structural & molecular biology · 2019Article
- cAMP binds to closed, inactivated, and open sea urchin HCN channels in a state-dependent manner.The Journal of general physiology · 2019Article
- All four subunits of HCN2 channels contribute to the activation gating in an additive but intricate manner.The Journal of general physiology · 2018Article
- Activation gating in HCN2 channels.PLoS computational biology · 2018Article
- HCN Channel C-Terminal Region Speeds Activation Rates Independently of Autoinhibition.The Journal of membrane biology · 2015Article
- Conformational Flip of Nonactivated HCN2 Channel Subunits Evoked by Cyclic Nucleotides.Biophysical journal · 2015Article
- Ion channel engineering: perspectives and strategies.Journal of molecular biology · 2015Review
- State-dependent and site-directed photodynamic transformation of HCN2 channel by singlet oxygen.The Journal of general physiology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are activated by membrane hyperpolarizations that cause an inward movement of the positive charges in the fourth transmembrane domain (S4), which triggers channel opening. The mechanism of how the motion of S4 charges triggers channel opening is unknown. Here, we used voltage clamp fluorometry (VCF) to detect S4 conformational changes and to correlate these to the different activation steps in spHCN channels. We show that S4 undergoes two distinct conformational changes during voltage activation. Analysis of the fluorescence signals suggests that the N-terminal region of S4 undergoes conformational changes during a previously characterized mode shift in HCN channel voltage dependence, while a more C-terminal region undergoes an additional conformational change during gating charge movements. We fit our fluorescence and ionic current data to a previously proposed 10-state allosteric model for HCN channels. Our results are not compatible with a fast S4 motion and rate-limiting channel opening. Instead, our data and modeling suggest that spHCN channels open after only two S4s have moved and that S4 motion is rate limiting during voltage activation of spHCN channels.
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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.