ArticleBiophysical journal2008
Gating consequences of charge neutralization of arginine residues in the S4 segment of K(v)7.2, an epilepsy-linked K+ channel subunit.
Article in Biophysical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 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
- Two-step voltage-sensor activation of the human KNature communications · 2026Article
- Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.Communications biology · 2024Article
- Distinctive mechanisms of epilepsy-causing mutants discovered by measuring S4 movement in KCNQ2 channels.eLife · 2022Article
- Molecular Insights Into Binding and Activation of the Human KCNQ2 Channel by Retigabine.Frontiers in molecular biosciences · 2022Article
- Structural Mechanism of ω-Currents in a Mutated Kv7.2 Voltage Sensor Domain from Molecular Dynamics Simulations.Journal of chemical information and modeling · 2021Article
- Combining endocannabinoids with retigabine for enhanced M-channel effect and improved KV7 subtype selectivity.The Journal of general physiology · 2020Article
- Polyunsaturated Fatty Acids as Modulators of KFrontiers in physiology · 2020Review
- Epileptic Encephalopathy In A Patient With A Novel Variant In The Kv7.2 S2 Transmembrane Segment: Clinical, Genetic, and Functional Features.International journal of molecular sciences · 2019Article
- Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening.The Journal of general physiology · 2019Article
- Key role of segment IS4 in Cav1.2 inactivation: link between activation and inactivation.Pflugers Archiv : European journal of physiology · 2017Article
- Infantile spasms and encephalopathy without preceding neonatal seizures caused by KCNQ2 R198Q, a gain-of-function variant.Epilepsia · 2017Article
- Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Gating pore currents are defects in common with two Nav1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy.The Journal of general physiology · 2015Article
- Molecular pathophysiology and pharmacology of the voltage-sensing module of neuronal ion channels.Frontiers in cellular neuroscience · 2015Review
- Capturing distinct KCNQ2 channel resting states by metal ion bridges in the voltage-sensor domain.The Journal of general physiology · 2014Article
- Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of K(v)7.2 potassium channel subunits.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- KCNQ1 channels do not undergo concerted but sequential gating transitions in both the absence and the presence of KCNE1 protein.The Journal of biological chemistry · 2012Article
- Transfer of Kv3.1 voltage sensor features to the isolated Ci-VSP voltage-sensing domain.Biophysical journal · 2012Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The K(v)7.2 subunits are the main molecular determinants of the M-current, a widespread K(+) current regulating neuronal excitability. Mutations in the K(v)7.2 gene cause benign familial neonatal seizures, an autosomally inherited human epilepsy. The benign familial neonatal seizure-causing mutations include those at arginine residues at positions 207 and 214 in the S(4) segment of K(v)7.2. In this study, each of the six S(4) arginines was individually replaced with neutral glutamines, and the functional properties of mutant channels were studied by whole-cell and single-channel voltage-clamp measurements. The results obtained suggest that each S(4) arginine residue plays a relevant role in the voltage-dependent gating of K(v)7.2 channels. In particular, a decreased positive charge at the N-terminal end of S(4) stabilized the activated state of the voltage-sensor, whereas positive-charge neutralization at the C-terminal end of S(4) favored the resting conformation. Strikingly, neutralization of a single arginine at position 201 was sufficient to cause a significant loss of voltage dependence in channel activation. Moreover, by comparing the functional properties of glutamine versus tryptophan substitution, we found steric bulk to play a relevant role at position 207, but not at position 214, in which the main functional effect of this disease-causing mutation seems to be a consequence of the loss of the positive charge.
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