ArticleThe Journal of general physiology2006
Reversal of HCN channel voltage dependence via bridging of the S4-S5 linker and Post-S6.
Article in The Journal of general physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Towards a unified gating scheme for the CNBD ion channel family.The Journal of general physiology · 2026Review
- An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels.bioRxiv : the preprint server for biology · 2025Article
- Mapping the contribution of the C-linker domain to gating polarity in CNBD channels.Biophysical journal · 2024Article
- Structural basis for hyperpolarization-dependent opening of human HCN1 channel.Nature communications · 2024Article
- Structural Basis for Hyperpolarization-dependent Opening of the Human HCN1 Channel.bioRxiv : the preprint server for biology · 2023Article
- Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels.Communications biology · 2022Article
- Electromechanical coupling mechanism for activation and inactivation of an HCN channel.Nature communications · 2021Article
- Cytoplasmic Autoinhibition in HCN Channels is Regulated by the Transmembrane Region.The Journal of membrane biology · 2020Article
- 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
- 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
- Dynamic rearrangement of the intrinsic ligand regulates KCNH potassium channels.The Journal of general physiology · 2018Article
- Structural insights into the mechanisms of CNBD channel function.The Journal of general physiology · 2018Review
- A new mechanism of voltage-dependent gating exposed by KThe Journal of general physiology · 2017Article
- hERG S4-S5 linker acts as a voltage-dependent ligand that binds to the activation gate and locks it in a closed state.Scientific reports · 2017Article
- HCN Channel C-Terminal Region Speeds Activation Rates Independently of Autoinhibition.The Journal of membrane biology · 2015Article
- Conservation analysis of residues in the S4-S5 linker and the terminal part of the S5-P-S6 pore modulus in Kv and HCN channels: flexible determinants for the electromechanical coupling.Pflugers Archiv : European journal of physiology · 2015Article
- Molecular pathophysiology and pharmacology of the voltage-sensing module of neuronal ion channels.Frontiers in cellular neuroscience · 2015Review
- State-dependent and site-directed photodynamic transformation of HCN2 channel by singlet oxygen.The Journal of general physiology · 2014Article
- Trans-activation response (TAR) RNA-binding protein 2 is a novel modulator of transient receptor potential canonical 4 (TRPC4) protein.The Journal of biological chemistry · 2014Article
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Authors and funding
2 authors.
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Abstract
Voltage-gated ion channels possess charged domains that move in response to changes in transmembrane voltage. How this movement is transduced into gating of the channel pore is largely unknown. Here we show directly that two functionally important regions of the spHCN1 pacemaker channel, the S4-S5 linker and the C-linker, come into close proximity during gating. Cross-linking these regions with high-affinity metal bridges or disulfide bridges dramatically alters channel gating in the absence of cAMP; after modification the polarity of voltage dependence is reversed. Instead of being closed at positive voltage and activating with hyperpolarization, modified channels are closed at negative voltage and activate with depolarization. Mechanistically, this reversal of voltage dependence occurs as a result of selectively eliminating channel deactivation, while retaining an existing inactivation process. Bridging also alters channel activation by cAMP, showing that interaction of these two regions can also affect the efficacy of physiological ligands.
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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.