ArticleThe Journal of general physiology2013
Flavonoid regulation of EAG1 channels.
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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Who cites it
29 citing papers in PubMed, 34 citations in OpenAlex.
- Lipid-dependent regulation of Kv10.1 in cancer: implications of membrane remodeling for channel function and pharmacology.Frontiers in pharmacology · 2026Review
- Use of Surface Plasmon Resonance Technique for Studies of Inter-domain Interactions in Ion Channels.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Conformation-sensitive antibody reveals an altered cytosolic PAS/CNBh assembly during hERG channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains.Channels (Austin, Tex.) · 2020Review
- Diversity of voltage-gated potassium channels and cyclic nucleotide-binding domain-containing channels in eukaryotes.Scientific reports · 2020Article
- Chlorpromazine binding to the PAS domains uncovers the effect of ligand modulation on EAG channel activity.The Journal of biological chemistry · 2020Article
- Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy.Frontiers in pharmacology · 2020Review
- Intestinal peroxisomal fatty acid β-oxidation regulates neural serotonin signaling through a feedback mechanism.PLoS biology · 2019Article
- Paul F. Cranefield Award to Anne E. Carlson.The Journal of general physiology · 2019Article
- Identification of undecylenic acid as EAG channel inhibitor using surface plasmon resonance-based screen of KCNH channels.BMC pharmacology & toxicology · 2019Article
- N- and C-terminal interactions in KCNH channels: The spotlight on the intrinsic ligand.The Journal of general physiology · 2019Article
- Bipolar switching by HCN voltage sensor underlies hyperpolarization activation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Evolution and Structural Characteristics of Plant Voltage-Gated KThe Plant cell · 2018Review
- Sperm Sensory Signaling.Cold Spring Harbor perspectives in biology · 2017Review
- Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects.British journal of pharmacology · 2017Article
- Eag1 Voltage-Dependent Potassium Channels: Structure, Electrophysiological Characteristics, and Function in Cancer.The Journal of membrane biology · 2017Review
- The intrinsically liganded cyclic nucleotide-binding homology domain promotes KCNH channel activation.The Journal of general physiology · 2017Article
- Investigating cyclic nucleotide and cyclic dinucleotide binding to HCN channels by surface plasmon resonance.PloS one · 2017Article
- Screening for Non-Pore-Binding Modulators of EAG K+ Channels.Journal of biomolecular screening · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The voltage-gated, K(+)-selective ether á go-go 1 (EAG1) channel is expressed throughout the brain where it is thought to regulate neuronal excitability. Besides its normal physiological role in the brain, EAG1 is abnormally expressed in several cancer cell types and promotes tumor progression. Like all other channels in the KCNH family, EAG1 channels have a large intracellular carboxy-terminal region that shares structural similarity with cyclic nucleotide-binding homology domains (CNBHDs). EAG1 channels, however, are not regulated by the direct binding of cyclic nucleotides and have no known endogenous ligands. In a screen of biological metabolites, we have now identified four flavonoids as potentiators of EAG1 channels: fisetin, quercetin, luteolin, and kaempferol. These four flavonoids shifted the voltage dependence of activation toward more hyperpolarizing potentials and slowed channel deactivation. All four flavonoids regulated channel gating with half-maximal concentrations of 2-8 µM. The potentiation of gating did not require the amino-terminal or post-CNBHD regions of EAG1 channels. However, in fluorescence resonance energy transfer and anisotropy-based binding assays, flavonoids bound to the purified CNBHD of EAG1 channels. The CNBHD of KCNH channels contains an intrinsic ligand, a conserved stretch of residues that occupy the cyclic nucleotide-binding pocket. Mutations of the intrinsic ligand in EAG1 (Y699A) potentiated gating similar to flavonoids, and flavonoids did not further potentiate EAG1-Y699A channels. Furthermore, the Y699A mutant CNBHD bound to flavonoids with higher affinity than wild-type CNBHD. These results suggest that the flavonoids identified here potentiated EAG1 channels by binding to the CNBHD, possibly by displacing their intrinsic ligand. EAG1 channels should be considered as a possible target for the physiological effects of flavonoids.
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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.