ArticleChemical research in toxicology2012
Marine algal toxin azaspiracid is an open-state blocker of hERG potassium channels.
Article in Chemical research in toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 81 citations in OpenAlex.
- "Algal-dromes": a novel conceptual approach to illness in humans exposed to harmful algal bloom toxins.Frontiers in toxicology · 2026Review
- High Affinity Aptamers and Their Specificity for Azaspiracid-2 Using Capture-SELEX.Marine drugs · 2025Article
- The Chemistry of Phytoplankton.Chemical reviews · 2024Review
- Current Research Status of Azaspiracids.Marine drugs · 2024Review
- Current Trends and New Challenges in Marine Phycotoxins.Marine drugs · 2022Review
- Industrial Applications of Dinoflagellate Phycotoxins Based on Their Modes of Action: A Review.Toxins · 2020Review
- Drug-likeness of linear pentamidine analogues and their impact on the hERG KRSC advances · 2019Article
- Biological Effects of the Azaspiracid-Producing DinoflagellateMarine drugs · 2019Article
- Effects of Temperature, Growth Media, and Photoperiod on Growth and Toxin Production ofMarine drugs · 2019Article
- Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions.Marine drugs · 2019Article
- Review
- Review
- Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates.Marine drugs · 2017Review
- Natural products modulating the hERG channel: heartaches and hope.Natural product reports · 2017Review
- Compilation and physicochemical classification analysis of a diverse hERG inhibition database.Journal of computer-aided molecular design · 2016Article
- Subacute Cardiovascular Toxicity of the Marine Phycotoxin Azaspiracid-1 in Rats.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Algal Toxin Azaspiracid-1 Induces Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry.Marine drugs · 2015Article
- Xenopus borealis as an alternative source of oocytes for biophysical and pharmacological studies of neuronal ion channels.Scientific reports · 2015Article
- New insights into the causes of human illness due to consumption of azaspiracid contaminated shellfish.Scientific reports · 2015Article
- In vitro chronic effects on hERG channel caused by the marine biotoxin azaspiracid-2.Toxicon : official journal of the International Society on Toxinology · 2014Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in shellfish and represent an emerging human health risk. Although human exposure is primarily manifested by severe and protracted diarrhea, this toxin class has been shown to be highly cytotoxic, a teratogen to developing fish, and a possible carcinogen in mice. Until now, AZA's molecular target has not yet been determined. Using three independent methods (voltage clamp, channel binding assay, and thallium flux assay), we have for the first time demonstrated that AZA1, AZA2, and AZA3 each bind to and block the hERG (human ether-à-go-go related gene) potassium channel heterologously expressed in HEK-293 mammalian cells. Inhibition of K(+) current for each AZA analogue was concentration-dependent (IC(50) value range: 0.64-0.84 μM). The mechanism of hERG channel inhibition by AZA1 was investigated further in Xenopus oocytes where it was shown to be an open-state-dependent blocker and, using mutant channels, to interact with F656 but not with Y652 within the S6 transmembrane domain that forms the channel's central pore. AZA1, AZA2, and AZA3 were each shown to inhibit [(3)H]dofetilide binding to the hERG channel and thallium ion flux through the channel (IC(50) value range: 2.1-6.6 μM). AZA1 did not block the K(+) current of the closely related EAG1 channel. Collectively, these data suggest that the AZAs physically block the K(+) conductance pathway of hERG1 channels by occluding the cytoplasmic mouth of the open pore. Although the concentrations necessary to block hERG channels are relatively high, AZA-induced blockage may prove to contribute to the toxicological properties of the AZAs.
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