ArticleProceedings of the National Academy of Sciences of the United States of America2009
Sequential formation of ion pairs during activation of a sodium channel voltage sensor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed.
- Voltage-sensing domains: structural and functional diversity.European biophysics journal : EBJ · 2026Review
- Voltage sensors.Molecular pharmacology · 2025Review
- Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.Communications biology · 2024Article
- The chemistry of electrical signaling in sodium channels from bacteria and beyond.Cell chemical biology · 2024Review
- Dynamics of activation in the voltage-sensing domain of Ciona intestinalis phosphatase Ci-VSP.Nature communications · 2024Article
- Functional effects of drugs and toxins interacting with NaFrontiers in pharmacology · 2024Review
- Non-canonical helical transitions and conformational switching are associated with characteristic flexibility and disorder indices in TRP and Kv channels.Channels (Austin, Tex.) · 2023Article
- Article
- Polycystin Channel Complexes.Annual review of physiology · 2023Review
- Activation and closed-state inactivation mechanisms of the human voltage-gated KMolecular cell · 2022Article
- The 70-year search for the voltage-sensing mechanism of ion channels.The Journal of physiology · 2022Article
- Nanosecond Pulsed Electric Field (nsPEF): Opening the Biotechnological Pandora's Box.International journal of molecular sciences · 2022Review
- Spliced isoforms of the cardiac Nav1.5 channel modify channel activation by distinct structural mechanisms.The Journal of general physiology · 2022Article
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Charge substitutions at the voltage-sensing module of domain III enhance actions of site-3 and site-4 toxins on an insect sodium channel.Insect biochemistry and molecular biology · 2021Article
- Voltage-dependent structural models of the human Hv1 proton channel from long-timescale molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structure of the Cardiac Sodium Channel.Cell · 2020Article
- Voltage-dependent gating in K channels: experimental results and quantitative models.Pflugers Archiv : European journal of physiology · 2020Review
- KCNQs: Ligand- and Voltage-Gated Potassium Channels.Frontiers in physiology · 2020Review
- Roles for Countercharge in the Voltage Sensor Domain of Ion Channels.Frontiers in pharmacology · 2020Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
Electrical signaling in biology depends upon a unique electromechanical transduction process mediated by the S4 segments of voltage-gated ion channels. These transmembrane segments are driven outward by the force of the electric field on positively charged amino acid residues termed "gating charges," which are positioned at three-residue intervals in the S4 transmembrane segment, and this movement is coupled to opening of the pore. Here, we use the disulfide-locking method to demonstrate sequential ion pair formation between the fourth gating charge in the S4 segment (R4) and two acidic residues in the S2 segment during activation. R4 interacts first with E70 at the intracellular end of the S2 segment and then with D60 near the extracellular end. Analysis with the Rosetta Membrane method reveals the 3-D structures of the gating pore as these ion pairs are formed sequentially to catalyze the S4 transmembrane movement required for voltage-dependent activation. Our results directly demonstrate sequential ion pair formation that is an essential feature of the sliding helix model of voltage sensor function but is not compatible with the other widely discussed gating models.
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