ArticleProceedings of the National Academy of Sciences of the United States of America2017
PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- PIPNature communications · 2026Article
- Two-step voltage-sensor activation of the human KNature communications · 2026Article
- A Historical Outline of Fluorescence Spectroscopy in Ion Channel Research.Advances in experimental medicine and biology · 2026Review
- Biophysical and structural mechanisms of epilepsy-associated mutations in the S4-S5 Linker of KCNQ2 channels.Channels (Austin, Tex.) · 2025Article
- Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.Cell research · 2025Article
- PIPResearch square · 2025Article
- Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Constitutive opening of the Kv7.2 pore activation gate causesProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.Communications biology · 2024Article
- Targeting the ICirculation research · 2024Article
- Ligand activation mechanisms of human KCNQ2 channel.Nature communications · 2023Article
- Ancient medicinal plant rosemary contains a highly efficacious and isoform-selective KCNQ potassium channel opener.Communications biology · 2023Article
- The toxic natural product tutin causes epileptic seizures in mice by activating calcineurin.Signal transduction and targeted therapy · 2023Article
- Electro-mechanical coupling of KCNQ channels is a target of epilepsy-associated mutations and retigabine.Science advances · 2022Article
- HumanJournal of neurophysiology · 2022Article
- Distinctive mechanisms of epilepsy-causing mutants discovered by measuring S4 movement in KCNQ2 channels.eLife · 2022Article
- Gain of function due to increased opening probability by twoProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- PIPCommunications biology · 2021Article
- From Bench to Biomolecular Simulation: Phospholipid Modulation of Potassium Channels.Journal of molecular biology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retigabine (RTG) is a first-in-class antiepileptic drug that suppresses neuronal excitability through the activation of voltage-gated KCNQ2-5 potassium channels. Retigabine binds to the pore-forming domain, causing a hyperpolarizing shift in the voltage dependence of channel activation. To elucidate how the retigabine binding site is coupled to changes in voltage sensing, we used voltage-clamp fluorometry to track conformational changes of the KCNQ3 voltage-sensing domains (VSDs) in response to voltage, retigabine, and PIP2. Steady-state ionic conductance and voltage sensor fluorescence closely overlap under basal PIP2 conditions. Retigabine stabilizes the conducting conformation of the pore and the activated voltage sensor conformation, leading to dramatic deceleration of current and fluorescence deactivation, but these effects are attenuated upon disruption of channel:PIP2 interactions. These findings reveal an important role for PIP2 in coupling retigabine binding to altered VSD function. We identify a polybasic motif in the proximal C terminus of retigabine-sensitive KCNQ channels that contributes to VSD-pore coupling via PIP2, and thereby influences the unique gating effects of retigabine.
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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.