ArticleThe Journal of general physiology2013
A point mutation in the human Slo1 channel that impairs its sensitivity to omega-3 docosahexaenoic acid.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Cholesterol and docosahexaenoic acid likely protect against alcohol-induced constriction of cerebral arteries via a common pathway.Advances in drug and alcohol research · 2026Article
- Docosahexaenoic acid protects against alcohol-induced constriction of cerebral arteries and inhibition of vascular smooth muscle BK channels.Alcohol, clinical & experimental research · 2025Article
- Incorporating physics to overcome data scarcity in predictive modeling of protein function: A case study of BK channels.PLoS computational biology · 2023Article
- Incorporating physics to overcome data scarcity in predictive modeling of protein function: a case study of BK channels.bioRxiv : the preprint server for biology · 2023Article
- Structural determinants of acid-sensing ion channel potentiation by single chain lipids.The Journal of general physiology · 2022Article
- Perspectives on Potential Fatty Acid Modulations of Motility Associated Human Sperm Ion Channels.International journal of molecular sciences · 2022Review
- Identification of PUFA interaction sites on the cardiac potassium channel KCNQ1.The Journal of general physiology · 2021Article
- Dietary fats and cardiometabolic disease: mechanisms and effects on risk factors and outcomes.Nature reviews. Cardiology · 2019Review
- Mechanisms of BK Channel Activation by Docosahexaenoic Acid in Rat Coronary Arterial Smooth Muscle Cells.Frontiers in pharmacology · 2018Article
- Article
- Differential efficacy of GoSlo-SR compounds on BKα and BKαγChannels (Austin, Tex.) · 2017Article
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
- Atomic determinants of BK channel activation by polyunsaturated fatty acids.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A.Marine drugs · 2016Article
- Effects of unsaturated fatty acids on the kinetics of voltage-gated proton channels heterologously expressed in cultured cells.The Journal of physiology · 2016Article
- 2014 Conway review lecture, Royal Academy of Medicine in Ireland: “S6, drugs and RCK and Bowl”.Irish journal of medical science · 2016Review
- In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on KFrontiers in physiology · 2016Review
- Single Channel Recordings Reveal Differential β2 Subunit Modulations Between Mammalian and Drosophila BKCa(β2) Channels.PloS one · 2016Article
- Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function.Frontiers in physiology · 2016Review
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5 authors at 3 institutions in 3 countries.
Funding
Abstract
Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA) at nanomolar concentrations reversibly activate human large-conductance Ca(2+)- and voltage-gated K(+) (Slo1 BK) channels containing auxiliary β1 or β4 subunits in cell-free patches. Here we examined the action of DHA on the Slo1 channel without any auxiliary subunit and sought to elucidate the biophysical mechanism and the molecular determinants of the DHA sensitivity. Measurements of ionic currents through human Slo1 (hSlo1) channels reveal that the stimulatory effect of DHA does not require activation of the voltage or Ca(2+) sensors. Unlike gating of the hSlo1 channel, that of the Drosophila melanogaster Slo1 (dSlo1) channel is unaltered by DHA. Our mutagenesis study based on the differential responses of human and dSlo1 channels to DHA pinpoints that Y318 near the cytoplasmic end of S6 in the hSlo1 channel is a critical determinant of the stimulatory action of DHA. The mutation Y318S in hSlo1, which replaces Y with S as found in dSlo1, greatly diminishes the channel's response to DHA with a 22-carbon chain whether β1 or β4 is absent or present. However, the responses to α-linolenic acid, an omegea-3 fatty acid with an 18-carbon chain, and to arachidonic acid, an omega-6 fatty acid with a 20-carbon chain, remain unaffected by the mutation. Y318 in the S6 segment of hSlo1 is thus an important determinant of the electrophysiological response of the channel to DHA. Furthermore, the mutation Y318S may prove to be useful in dissecting out the complex lipid-mediated modulation of Slo1 BK channels.
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