title: In vitro chronic effects on hERG channel caused by the marine biotoxin azaspiracid-2.
abstract: Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellate Azadinium spinosum that accumulate in many shellfish species. Azaspiracid poisoning caused by AZA-contaminated seafood consumption is primarily manifested by diarrhea in humans. To protect human health, AZA-1, AZA-2 and AZA-3 content in seafood has been regulated by food safety authorities in many countries. Recently AZAs have been reported as a low/moderate hERG channel blockers. Furthermore AZA-2 has been related to arrhythmia appearance in rats, suggesting potential heart toxicity. In this study AZA-2 in vitro effects on hERG channel after chronic exposure are analyzed to further explore potential cardiotoxicity. The amount of hERG channel in the plasma membrane, hERG channel trafficking and hERG currents were evaluated up to 12 h of toxin exposure. In these conditions AZA-2 caused an increase of hERG levels in the plasma membrane, probably related to hERG retrograde trafficking impairment. Although this alteration did not translate into an increase of hERG channel-related current, more studies will be necessary to understand its mechanism and to know what consequences could have in vivo. These findings suggest that azaspiracids might have chronic cardiotoxicity related to hERG channel trafficking and they should not be overlooked when evaluating the threat to human health.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain.
authors.forename: Sara F
authors.initials: SF
authors.lastname: Ferreiro
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: natalia.vilarino@usc.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vilariño
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Louzao
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Frederick
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: luis.botana@usc.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects*; D005663:Furans / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008387:Marine Toxins / Q000633:toxicity*; D018408:Patch-Clamp Techniques; D011714:Pyrans / Q000633:toxicity*; D000095702:Polyether Toxins
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005663:Furans; D008387:Marine Toxins; D011714:Pyrans; C000606913:KCNH2 protein, human; C520447:azaspiracid-2; D000095702:Polyether Toxins
keywords: Automated patch clamp; Azaspiracid; Cardiotoxicity; Chronic; Trafficking; hERG