ArticleThe Journal of general physiology2011
Mode shift of the voltage sensors in Shaker K+ channels is caused by energetic coupling to the pore domain.
Article in The Journal of general physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 79 citations in OpenAlex.
- Structural and kinetic mechanisms of state-dependent potassium channel inhibition.Science advances · 2026Article
- Molecular Determinants of Voltage-Dependent Gating in Kv11.1 Channels.Advances in experimental medicine and biology · 2026Review
- A Historical Outline of Fluorescence Spectroscopy in Ion Channel Research.Advances in experimental medicine and biology · 2026Review
- Closed state structure of the pore revealed by uncoupled Shaker KNature communications · 2025Article
- Voltage gating and 4-aminopyridine inhibition in the Shaker Kv channel revealed by a closed-state model.Biophysical journal · 2025Article
- Energy landscape of a Kv channel revealed by temperature steps while perturbing its electromechanical coupling.Nature communications · 2025Article
- KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1.International journal of molecular sciences · 2024Article
- Beta-Barrel Channel Response to High Electric Fields: Functional Gating or Reversible Denaturation?International journal of molecular sciences · 2023Article
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Charge-voltage curves of Shaker potassium channel are not hysteretic at steady state.The Journal of general physiology · 2023Article
- Mapping Electromechanical Coupling Pathways in Voltage-Gated Ion Channels: Challenges and the Way Forward.Journal of molecular biology · 2021Review
- A Common Kinetic Property of Mutations Linked to Episodic Ataxia Type 1 Studied in the Shaker Kv Channel.International journal of molecular sciences · 2020Article
- Voltage-dependent gating in K channels: experimental results and quantitative models.Pflugers Archiv : European journal of physiology · 2020Review
- Modulation of hERG KFrontiers in pharmacology · 2020Review
- Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating.eLife · 2019Article
- Simulation of Gating Currents of the Shaker K Channel Using a Brownian Model of the Voltage Sensor.Biophysical journal · 2019Article
- The contribution of voltage clamp fluorometry to the understanding of channel and transporter mechanisms.The Journal of general physiology · 2019Review
- Extracellular protons accelerate hERG channel deactivation by destabilizing voltage sensor relaxation.The Journal of general physiology · 2019Article
- S4-S5 linker movement during activation and inactivation in voltage-gated KProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
2 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 2 countries.
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Abstract
The voltage sensors of voltage-gated ion channels undergo a conformational change upon depolarization of the membrane that leads to pore opening. This conformational change can be measured as gating currents and is thought to be transferred to the pore domain via an annealing of the covalent link between voltage sensor and pore (S4-S5 linker) and the C terminus of the pore domain (S6). Upon prolonged depolarizations, the voltage dependence of the charge movement shifts to more hyperpolarized potentials. This mode shift had been linked to C-type inactivation but has recently been suggested to be caused by a relaxation of the voltage sensor itself. In this study, we identified two ShakerIR mutations in the S4-S5 linker (I384N) and S6 (F484G) that, when mutated, completely uncouple voltage sensor movement from pore opening. Using these mutants, we show that the pore transfers energy onto the voltage sensor and that uncoupling the pore from the voltage sensor leads the voltage sensors to be activated at more negative potentials. This uncoupling also eliminates the mode shift occurring during prolonged depolarizations, indicating that the pore influences entry into the mode shift. Using voltage-clamp fluorometry, we identified that the slow conformational change of the S4 previously correlated with the mode shift disappears when uncoupling the pore. The effects can be explained by a mechanical load that is imposed upon the voltage sensors by the pore domain and allosterically modulates its conformation. Mode shift is caused by the stabilization of the open state but leads to a conformational change in the voltage sensor.
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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.