ArticleCell research2013
The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands.
Article in Cell research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed.
- Voltage-sensor conformational microenvironments encode isoform-selective ion channel activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mapping the knowledge of epilepsy and Potassium Channels: A scientometric analysis in CiteSpace and VOSviewer.IBRO neuroscience reports · 2025Article
- Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology.Molecular neurobiology · 2024Review
- Site and Mechanism of ML252 Inhibition of Kv7 Voltage-Gated Potassium Channels.Function (Oxford, England) · 2023Article
- A novelMolecular medicine reports · 2022Article
- Triclosan is a KCNQ3 potassium channel activator.Pflugers Archiv : European journal of physiology · 2022Article
- Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021Review
- Resin-acid derivatives bind to multiple sites on the voltage-sensor domain of the Shaker potassium channel.The Journal of general physiology · 2021Article
- Molecular basis for ligand activation of the human KCNQ2 channel.Cell research · 2021Article
- Coupling stabilizers open KProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Chemical regulation of Kv7 channels: Diverse scaffolds, sites, and mechanisms of action.The Journal of general physiology · 2020Article
- Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels.Acta pharmacologica Sinica · 2020Article
- Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5.Biomolecules · 2019Review
- Cell-Free Expression of Sodium Channel Domains for Pharmacology Studies. Noncanonical Spider Toxin Binding Site in the Second Voltage-Sensing Domain of Human NaFrontiers in pharmacology · 2019Article
- Pore- and voltage sensor-targeted KCNQ openers have distinct state-dependent actions.The Journal of general physiology · 2018Article
- One drug-sensitive subunit is sufficient for a near-maximal retigabine effect in KCNQ channels.The Journal of general physiology · 2018Article
- Four drug-sensitive subunits are required for maximal effect of a voltage sensor-targeted KCNQ opener.The Journal of general physiology · 2018Article
- Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors.The Journal of general physiology · 2018Article
- In silico identification of small molecules as novel LXR agonists for the treatment of cardiovascular disease and cancer.Journal of molecular modeling · 2018Article
Corrections and comments
- Commented on by
Authors and funding
10 authors.
Funding
Abstract
Voltage-gated potassium (Kv) channels derive their voltage sensitivity from movement of gating charges in voltage-sensor domains (VSDs). The gating charges translocate through a physical pathway in the VSD to open or close the channel. Previous studies showed that the gating charge pathways of Shaker and Kv1.2-2.1 chimeric channels are occluded, forming the structural basis for the focused electric field and gating charge transfer center. Here, we show that the gating charge pathway of the voltage-gated KCNQ2 potassium channel, activity reduction of which causes epilepsy, can accommodate various small molecule ligands. Combining mutagenesis, molecular simulation and electrophysiological recording, a binding model for the probe activator, ztz240, in the gating charge pathway was defined. This information was used to establish a docking-based virtual screening assay targeting the defined ligand-binding pocket. Nine activators with five new chemotypes were identified, and in vivo experiments showed that three ligands binding to the gating charge pathway exhibit significant anti-epilepsy activity. Identification of various novel activators by virtual screening targeting the pocket supports the presence of a ligand-binding site in the gating charge pathway. The capability of the gating charge pathway to accommodate small molecule ligands offers new insights into the gating charge pathway of the therapeutically relevant KCNQ2 channel.
Indexed as
Identifiers
What OpenQuestion holds
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.