ArticleProceedings of the National Academy of Sciences of the United States of America2015
Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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Who cites it
57 citing papers in PubMed, 88 citations in OpenAlex.
- Functions of the KCNE Gene Family in Ion Channels.Biochemical genetics · 2026Review
- A mechanistic understanding of how KCNE1 tunes KCNQ1 channel pharmacology.Structure (London, England : 1993) · 2026Article
- Conventional Antiarrhythmics Class I-IV, Late INa Inhibitors, IKs Enhancers, RyR2 Stabilizers, Gap Junction Modulators, Atrial-Selective Antiarrhythmics, and Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Therapy in Arrhythmias.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.Cell research · 2025Article
- Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.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 · 2025Article
- Influence of Olive Oil Components on Ion Channels.Molecules (Basel, Switzerland) · 2025Review
- Current and future precision therapy approaches in the long QT syndrome.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Article
- Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.Communications biology · 2024Article
- Targeting the ICirculation research · 2024Article
- Activation of hTREK-1 by polyunsaturated fatty acids involves direct interaction.Scientific reports · 2024Article
- Mechanistic understanding of KCNQ1 activating polyunsaturated fatty acid analogs.The Journal of general physiology · 2023Article
- Pharmacological Screening of Kv7.1 and Kv7.1/KCNE1 Activators as Potential Antiarrhythmic Drugs in the Zebrafish Heart.International journal of molecular sciences · 2023Article
- Mechanistic insights into robust cardiac IeLife · 2023Article
- Mechanism of external K+ sensitivity of KCNQ1 channels.The Journal of general physiology · 2023Article
- Long-QT mutations in KCNE1 modulate the 17β-estradiol response of Kv7.1/KCNE1.Science advances · 2023Article
- Mechanistic insights into robust cardiac IbioRxiv : the preprint server for biology · 2023Article
- Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural determinants of acid-sensing ion channel potentiation by single chain lipids.The Journal of general physiology · 2022Article
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pKa value, to preserve their negative charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.
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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 OpenQuestion graph.