ArticleThe Journal of general physiology2019
Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening.
Article in The Journal of general physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 16 citations in OpenAlex.
- Two-step voltage-sensor activation of the human KNature communications · 2026Article
- The conductance of KCNQ2 and its pathogenic variants is determined by individual subunit gating.Science advances · 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
- Glial KCNQ KNeuron · 2024Article
- Clinical analysis and functional characterization of KCNQ2-related developmental and epileptic encephalopathy.Frontiers in molecular neuroscience · 2023Article
- Electro-mechanical coupling of KCNQ channels is a target of epilepsy-associated mutations and retigabine.Science advances · 2022Article
- Distinctive mechanisms of epilepsy-causing mutants discovered by measuring S4 movement in KCNQ2 channels.eLife · 2022Article
Corrections and comments
- Commented on by
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
One of the major factors known to cause neuronal hyperexcitability is malfunction of the potassium channels formed by KCNQ2 and KCNQ3. These channel subunits underlie the M current, which regulates neuronal excitability. Here, I investigate the molecular mechanisms by which epilepsy-associated mutations in the voltage sensor (S4) of KCNQ3 cause channel malfunction. Voltage clamp fluorometry reveals that the R230C mutation in KCNQ3 allows S4 movement but shifts the open/closed transition of the gate to very negative potentials. This results in the mutated channel remaining open throughout the physiological voltage range. Substitution of R230 with natural and unnatural amino acids indicates that the functional effect of the arginine residue at position 230 depends on both its positive charge and the size of its side chain. I find that KCNQ3-R230C is hard to close, but it is capable of being closed at strong negative voltages. I suggest that compounds that shift the voltage dependence of S4 activation to more positive potentials would promote gate closure and thus have therapeutic potential.
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.