ArticleThe Journal of biological chemistry2012
KCNQ1 channels do not undergo concerted but sequential gating transitions in both the absence and the presence of KCNE1 protein.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Barium senses subtle pore changes in a voltage-gated KScience advances · 2026Article
- A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.Nature communications · 2025Article
- The conductance of KCNQ2 and its pathogenic variants is determined by individual subunit gating.Science advances · 2025Article
- Evaluating sequential and allosteric activation models in IKs channels with mutated voltage sensors.The Journal of general physiology · 2024Article
- Insights into Cardiac IKs (KCNQ1/KCNE1) Channels Regulation.International journal of molecular sciences · 2020Review
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers 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
- Article
- Gating modulation of the KCNQ1 channel by KCNE proteins studied by voltage-clamp fluorometry.Biophysics and physicobiology · 2019Review
- Effects of β-subunit on gating of a potassium ion channel: Molecular simulations of cardiac IKs activation.Journal of molecular and cellular cardiology · 2018Article
- Four drug-sensitive subunits are required for maximal effect of a voltage sensor-targeted KCNQ opener.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
- Modeling the Hidden Pathways of IKs Channel Activation.Biophysical journal · 2018Article
- The Structural Basis of IKs Ion-Channel Activation: Mechanistic Insights from Molecular Simulations.Biophysical journal · 2018Article
- Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1.Nature communications · 2018Article
- Inactivation gating of Kv7.1 channels does not involve concerted cooperative subunit interactions.Channels (Austin, Tex.) · 2018Article
- Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels.Biophysical journal · 2016Review
- Intersubunit Concerted Cooperative and cis-Type Mechanisms Modulate Allosteric Gating in Two-Pore-Domain Potassium Channel TREK-2.Frontiers in cellular neuroscience · 2016Article
- The KCNQ1 channel - remarkable flexibility in gating allows for functional versatility.The Journal of physiology · 2015Review
- Capturing distinct KCNQ2 channel resting states by metal ion bridges in the voltage-sensor domain.The Journal of general physiology · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The co-assembly of KCNQ1 with KCNE1 produces I(KS), a K(+) current, crucial for the repolarization of the cardiac action potential. Mutations in these channel subunits lead to life-threatening cardiac arrhythmias. However, very little is known about the gating mechanisms underlying KCNQ1 channel activation. Shaker channels have provided a powerful tool to establish the basic gating mechanisms of voltage-dependent K(+) channels, implying prior independent movement of all four voltage sensor domains (VSDs) followed by channel opening via a last concerted cooperative transition. To determine the nature of KCNQ1 channel gating, we performed a thermodynamic mutant cycle analysis by constructing a concatenated tetrameric KCNQ1 channel and by introducing separately a gain and a loss of function mutation, R231W and R243W, respectively, into the S4 helix of the VSD of one, two, three, and four subunits. The R231W mutation destabilizes channel closure and produces constitutively open channels, whereas the R243W mutation disrupts channel opening solely in the presence of KCNE1 by right-shifting the voltage dependence of activation. The linearity of the relationship between the shift in the voltage dependence of activation and the number of mutated subunits points to an independence of VSD movements, with each subunit incrementally contributing to channel gating. Contrary to Shaker channels, our work indicates that KCNQ1 channels do not experience a late cooperative concerted opening transition. Our data suggest that KCNQ1 channels in both the absence and the presence of KCNE1 undergo sequential gating transitions leading to channel opening even before all VSDs have moved.
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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.