ArticleJournal of cell science2014
Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP₂.
Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- C-terminal long-QT type 1 R562S-Kv7.1 variant, the first variant in helix C impairing β-adrenergic response of the slow delayed rectifier K+ channel.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Graded activation of mutant K41C-KCNE1:KCNQ1 channel complexes by mefenamic acid.Channels (Austin, Tex.) · 2025Article
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- Ventricular ion channels and arrhythmias: an overview of physiology, pathophysiology and pharmacology.Medical review (2021) · 2025Review
- Targeting the ICirculation research · 2024Article
- Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic β-cells.iScience · 2024Article
- The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel.Cancers · 2023Review
- Development of automated patch clamp assays to overcome the burden of variants of uncertain significance in inheritable arrhythmia syndromes.Frontiers in physiology · 2023Review
- Modulation of the IBBA advances · 2023Article
- Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277.Nature communications · 2022Article
- Article
- The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease.Frontiers in cardiovascular medicine · 2022Review
- Membrane pools of phosphatidylinositol-4-phosphate regulate KCNQ1/KCNE1 membrane expression.Communications biology · 2021Article
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Cardiac KHandbook of experimental pharmacology · 2021Review
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Neurohormonal Regulation of IJournal of the American Heart Association · 2020Review
- The unconventional biogenesis of Kv7.1-KCNE1 complexes.Science advances · 2020Article
- Physical and functional interaction sites in cytoplasmic domains of KCNQ1 and KCNE1 channel subunits.American journal of physiology. Heart and circulatory physiology · 2020Article
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
KCNQ1 and KCNE1 co-assembly generates the I(KS) K(+) current, which is crucial to the cardiac action potential repolarization. Mutations in their corresponding genes cause long QT syndrome (LQT) and atrial fibrillation. The A-kinase anchor protein, yotiao (also known as AKAP9), brings the I(KS) channel complex together with signaling proteins to achieve regulation upon β1-adrenergic stimulation. Recently, we have shown that KCNQ1 helix C interacts with the KCNE1 distal C-terminus. We postulated that this interface is crucial for I(KS) channel modulation. Here, we examined the yet unknown molecular mechanisms of LQT mutations located at this intracellular intersubunit interface. All LQT mutations disrupted the internal KCNQ1-KCNE1 intersubunit interaction. LQT mutants in KCNQ1 helix C led to a decreased current density and a depolarizing shift of channel activation, mainly arising from impaired phosphatidylinositol-4,5-bisphosphate (PIP2) modulation. In the KCNE1 distal C-terminus, the LQT mutation P127T suppressed yotiao-dependent cAMP-mediated upregulation of the I(KS) current, which was caused by reduced KCNQ1 phosphorylation at S27. Thus, KCNQ1 helix C is important for channel modulation by PIP2, whereas the KCNE1 distal C-terminus appears essential for the regulation of IKS by yotiao-mediated PKA phosphorylation.
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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 Socratic graph.