ArticleNature communications2015
Atomic basis for therapeutic activation of neuronal potassium channels.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 90 citations in OpenAlex.
- Voltage-sensor conformational microenvironments encode isoform-selective ion channel activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Discovery of E0199: A novel compound targeting both peripheral NaJournal of pharmaceutical analysis · 2025Article
- Plasticity of Mouse Dorsal Root Ganglion Neurons by Innate Immune Activation Is Influenced by Electrophysiological Activity.Journal of neurochemistry · 2025Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Discovery of a potent, Kv7.3-selective potassium channel opener from a Polynesian traditional botanical anticonvulsant.Communications chemistry · 2024Article
- In Silico Methods for the Discovery of Kv7.2/7.3 Channels Modulators: A Comprehensive Review.Molecules (Basel, Switzerland) · 2024Review
- The binding and mechanism of a positive allosteric modulator of Kv3 channels.Nature communications · 2024Article
- KJournal of pain research · 2024Article
- Dehydroepiandrosterone Sulfate (DHEAS) Is an Endogenous Kv7 Channel Modulator That Reduces Kv7/M-Current Suppression and Inflammatory Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Dual regulation of Kv7.2/7.3 channels by long-chain n-alcohols.The Journal of general physiology · 2023Article
- Site and Mechanism of ML252 Inhibition of Kv7 Voltage-Gated Potassium Channels.Function (Oxford, England) · 2023Article
- Development of an automated screen for Kv7.2 potassium channels and discovery of a new agonist chemotype.Bioorganic & medicinal chemistry letters · 2022Article
- Beyond Retigabine: Design, Synthesis, and Pharmacological Characterization of a Potent and Chemically Stable Neuronal Kv7 Channel Activator with Anticonvulsant Activity.Journal of medicinal chemistry · 2022Article
- Electro-mechanical coupling of KCNQ channels is a target of epilepsy-associated mutations and retigabine.Science advances · 2022Article
- Triclosan is a KCNQ3 potassium channel activator.Pflugers Archiv : European journal of physiology · 2022Article
- KCNQ Potassium Channels as Targets of Botanical Folk Medicines.Annual review of pharmacology and toxicology · 2022Review
- Molecular Insights Into Binding and Activation of the Human KCNQ2 Channel by Retigabine.Frontiers in molecular biosciences · 2022Article
- PIPCommunications biology · 2021Article
- The Amyloid Precursor Protein C99 Fragment Modulates Voltage-Gated Potassium Channels.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
Retigabine is a recently approved anticonvulsant that acts by potentiating neuronal M-current generated by KCNQ2-5 channels, interacting with a conserved Trp residue in the channel pore domain. Using unnatural amino-acid mutagenesis, we subtly altered the properties of this Trp to reveal specific chemical interactions required for retigabine action. Introduction of a non-natural isosteric H-bond-deficient Trp analogue abolishes channel potentiation, indicating that retigabine effects rely strongly on formation of a H-bond with the conserved pore Trp. Supporting this model, substitution with fluorinated Trp analogues, with increased H-bonding propensity, strengthens retigabine potency. In addition, potency of numerous retigabine analogues correlates with the negative electrostatic surface potential of a carbonyl/carbamate oxygen atom present in most KCNQ activators. These findings functionally pinpoint an atomic-scale interaction essential for effects of retigabine and provide stringent constraints that may guide rational improvement of the emerging drug class of KCNQ channel activators.
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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.