ArticlePloS one2012
Bisphenol A binds to the local anesthetic receptor site to block the human cardiac sodium channel.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- Review
- Comparative cardiotoxicity assessment of bisphenol chemicals and estradiol using human induced pluripotent stem cell-derived cardiomyocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Molecular Modeling of Cardiac Sodium Channel with Mexiletine.Membranes · 2022Article
- Natural Products in Mitigation of Bisphenol A Toxicity: Future Therapeutic Use.Molecules (Basel, Switzerland) · 2022Review
- Endocrine-Disrupting Effects of Bisphenol A on the Cardiovascular System: A Review.Journal of xenobiotics · 2022Review
- Characteristics of Bisphenol Cardiotoxicity: Impaired Excitability, Contractility, and Relaxation.Cardiovascular toxicology · 2022Review
- Local Anesthetic Like Inhibition of the Cardiac NaJournal of experimental pharmacology · 2022Article
- Article
- Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.Frontiers in pharmacology · 2022Review
- Structural modeling of NaBiophysics reports · 2021Article
- Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes.Birth defects research · 2020Review
- Noncanonical Ion Channel Behaviour in Pain.International journal of molecular sciences · 2019Review
- Article
- The citrus flavanone hesperetin preferentially inhibits slow-inactivating currents of a long QT syndrome type 3 syndrome NaBritish journal of pharmacology · 2019Article
- Disruption of neonatal cardiomyocyte physiology following exposure to bisphenol-a.Scientific reports · 2018Article
- Rapid and Sensitive SERS Detection of Bisphenol A Using Self-assembled Graphitic Substrates.Scientific reports · 2017Article
- Bisphenol A inhibits compound action potentials in the frog sciatic nerve in a manner independent of estrogen receptors.Biochemistry and biophysics reports · 2017Article
- Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.The Journal of general physiology · 2017Article
- Divergent Mechanisms Leading to Signaling Dysfunction in Embryonic Muscle by Bisphenol A and Tetrabromobisphenol A.Molecular pharmacology · 2017Article
- Modeling the human NaDrug design, development and therapy · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Bisphenol A (BPA) has attracted considerable public attention as it leaches from plastic used in food containers, is detectable in human fluids and recent epidemiologic studies link BPA exposure with diseases including cardiovascular disorders. As heart-toxicity may derive from modified cardiac electrophysiology, we investigated the interaction between BPA and hNav1.5, the predominant voltage-gated sodium channel subtype expressed in the human heart. Electrophysiology studies of heterologously-expressed hNav1.5 determined that BPA blocks the channel with a K(d) of 25.4±1.3 µM. By comparing the effects of BPA and the local anesthetic mexiletine on wild type hNav1.5 and the F1760A mutant, we demonstrate that both compounds share an overlapping binding site. With a key binding determinant thus identified, an homology model of hNav1.5 was generated based on the recently-reported crystal structure of the bacterial voltage-gated sodium channel NavAb. Docking predictions position both ligands in a cavity delimited by F1760 and contiguous with the DIII-IV pore fenestration. Steered molecular dynamics simulations used to assess routes of ligand ingress indicate that the DIII-IV pore fenestration is a viable access pathway. Therefore BPA block of the human heart sodium channel involves the local anesthetic receptor and both BPA and mexiletine may enter the closed-state pore via membrane-located side fenestrations.
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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.