ArticleThe Journal of general physiology2020
Polyunsaturated fatty acids produce a range of activators for heterogeneous IKs channel dysfunction.
Article in The Journal of general physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Gating shift to an ohmic mode of TREK-1 channel induced by docosahexaenoic acid.Biophysical journal · 2026Article
- Strategies for prolonging ventricular action potential duration without increasing transmural dispersion of repolarization.Physiological reports · 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
- Article
- Mechanistic understanding of KCNQ1 activating polyunsaturated fatty acid analogs.The Journal of general physiology · 2023Article
- Mechanistic insights into robust cardiac IeLife · 2023Article
- Mechanistic insights into robust cardiac IbioRxiv : the preprint server for biology · 2023Article
- Targeting ion channels with ultra-large library screening for hit discovery.Frontiers in molecular neuroscience · 2023Review
- ASIC3, a proton-gated ion channel with preference for polyunsaturated lipids with specific headgroup and tail properties.The Journal of general physiology · 2022Article
- Structural determinants of acid-sensing ion channel potentiation by single chain lipids.The Journal of general physiology · 2022Article
- Docosahexaenoic acid normalizes QT interval in long QT type 2 transgenic rabbit models in a genotype-specific fashion.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 · 2022Article
- Insights into Cardiac IKs (KCNQ1/KCNE1) Channels Regulation.International journal of molecular sciences · 2020Review
- Combining endocannabinoids with retigabine for enhanced M-channel effect and improved KV7 subtype selectivity.The Journal of general physiology · 2020Article
- Article
- Polyunsaturated Fatty Acids as Modulators of KFrontiers in physiology · 2020Review
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers in physiology · 2020Review
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6 authors at 2 institutions in 2 countries.
Funding
Abstract
Repolarization and termination of the ventricular cardiac action potential is highly dependent on the activation of the slow delayed-rectifier potassium IKs channel. Disruption of the IKs current leads to the most common form of congenital long QT syndrome (LQTS), a disease that predisposes patients to ventricular arrhythmias and sudden cardiac death. We previously demonstrated that polyunsaturated fatty acid (PUFA) analogues increase outward K+ current in wild type and LQTS-causing mutant IKs channels. Our group has also demonstrated the necessity of a negatively charged PUFA head group for potent activation of the IKs channel through electrostatic interactions with the voltage-sensing and pore domains. Here, we test whether the efficacy of the PUFAs can be tuned by the presence of different functional groups in the PUFA head, thereby altering the electrostatic interactions of the PUFA head group with the voltage sensor or the pore. We show that PUFA analogues with taurine and cysteic head groups produced the most potent activation of IKs channels, largely by shifting the voltage dependence of activation. In comparison, the effect on voltage dependence of PUFA analogues with glycine and aspartate head groups was half that of the taurine and cysteic head groups, whereas the effect on maximal conductance was similar. Increasing the number of potentially negatively charged moieties did not enhance the effects of the PUFA on the IKs channel. Our results show that one can tune the efficacy of PUFAs on IKs channels by altering the pKa of the PUFA head group. Different PUFAs with different efficacy on IKs channels could be developed into more personalized treatments for LQTS patients with a varying degree of IKs channel dysfunction.
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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.