{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:47:19Z","timestamp":1777636039064,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Campus Terra (USC)","award":["2022-PU011"],"award-info":[{"award-number":["2022-PU011"]}]},{"name":"Campus Terra (USC)","award":["2022-PU016"],"award-info":[{"award-number":["2022-PU016"]}]},{"name":"Campus Terra (USC)","award":["ED431C 2021\/01"],"award-info":[{"award-number":["ED431C 2021\/01"]}]},{"name":"Campus Terra (USC)","award":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"],"award-info":[{"award-number":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"]}]},{"name":"Campus Terra (USC)","award":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"],"award-info":[{"award-number":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"]}]},{"name":"Campus Terra (USC)","award":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"],"award-info":[{"award-number":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"]}]},{"name":"BreveRiesgo","award":["2022-PU011"],"award-info":[{"award-number":["2022-PU011"]}]},{"name":"BreveRiesgo","award":["2022-PU016"],"award-info":[{"award-number":["2022-PU016"]}]},{"name":"BreveRiesgo","award":["ED431C 2021\/01"],"award-info":[{"award-number":["ED431C 2021\/01"]}]},{"name":"BreveRiesgo","award":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"],"award-info":[{"award-number":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"]}]},{"name":"BreveRiesgo","award":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"],"award-info":[{"award-number":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"]}]},{"name":"BreveRiesgo","award":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"],"award-info":[{"award-number":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"]}]},{"name":"CLIMIGAL","award":["2022-PU011"],"award-info":[{"award-number":["2022-PU011"]}]},{"name":"CLIMIGAL","award":["2022-PU016"],"award-info":[{"award-number":["2022-PU016"]}]},{"name":"CLIMIGAL","award":["ED431C 2021\/01"],"award-info":[{"award-number":["ED431C 2021\/01"]}]},{"name":"CLIMIGAL","award":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"],"award-info":[{"award-number":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"]}]},{"name":"CLIMIGAL","award":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"],"award-info":[{"award-number":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"]}]},{"name":"CLIMIGAL","award":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"],"award-info":[{"award-number":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"]}]},{"name":"Conselleria de Cultura, Educacion e Ordenaci\u00f3n Universitaria, Xunta de Galicia, GRC","award":["2022-PU011"],"award-info":[{"award-number":["2022-PU011"]}]},{"name":"Conselleria de Cultura, Educacion e Ordenaci\u00f3n Universitaria, Xunta de Galicia, GRC","award":["2022-PU016"],"award-info":[{"award-number":["2022-PU016"]}]},{"name":"Conselleria de Cultura, Educacion e Ordenaci\u00f3n Universitaria, Xunta de Galicia, GRC","award":["ED431C 2021\/01"],"award-info":[{"award-number":["ED431C 2021\/01"]}]},{"name":"Conselleria de Cultura, Educacion e Ordenaci\u00f3n Universitaria, Xunta de Galicia, GRC","award":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"],"award-info":[{"award-number":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"]}]},{"name":"Conselleria de Cultura, Educacion e Ordenaci\u00f3n Universitaria, Xunta de Galicia, GRC","award":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"],"award-info":[{"award-number":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"]}]},{"name":"Conselleria de Cultura, Educacion e Ordenaci\u00f3n Universitaria, Xunta de Galicia, GRC","award":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"],"award-info":[{"award-number":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"]}]},{"name":"European Union","award":["2022-PU011"],"award-info":[{"award-number":["2022-PU011"]}]},{"name":"European Union","award":["2022-PU016"],"award-info":[{"award-number":["2022-PU016"]}]},{"name":"European Union","award":["ED431C 2021\/01"],"award-info":[{"award-number":["ED431C 2021\/01"]}]},{"name":"European Union","award":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"],"award-info":[{"award-number":["Interreg EAPA-0032\/2022\u2014BEAP-MAR"]}]},{"name":"European Union","award":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"],"award-info":[{"award-number":["HORIZON-MSCA-2022-DN-01-MSCA Doctoral Networks 2022 101119901-BIOTOXDoc"]}]},{"name":"European Union","award":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"],"award-info":[{"award-number":["HORIZON-CL6-2023-CIRCBIO-01 COMBO-101135438"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The growing concern about ciguatera fish poisoning (CF) due to the expansion of the microorganisms producing ciguatoxins (CTXs) increased the need to develop a reliable and fast method for ciguatoxin detection to guarantee food safety. Cytotoxicity assay on the N2a cells sensitized with ouabain (O) and veratridine (V) is routinely used in ciguatoxin detection; however, this method has not been standardized yet. This study demonstrated the low availability of sodium channels in the N2a cells, the great O\/V damage to the cells and the cell detachment when the cell viability is evaluated by the classical cytotoxicity assay and confirmed the absence of toxic effects caused by CTXs alone when using the methods that do not require medium removal such as lactate dehydrogenase (LDH) and Alamar blue assays. Different cell lines were evaluated as alternatives, such as human neuroblastoma, which was not suitable for the CTX detection due to the greater sensitivity to O\/V and low availability of sodium channels. However, the HEK293 Nav cell line expressing the \u03b11.6 subunit of sodium channels was sensitive to the ciguatoxin without the sensitization with O\/V due to its expression of sodium channels. In the case of sensitizing the cells with O\/V, it was possible to detect the presence of the ciguatoxin by the classical cytotoxicity MTT method at concentrations as low as 0.0001 nM CTX3C, providing an alternative cell line for the detection of compounds that act on the sodium channels.<\/jats:p>","DOI":"10.3390\/md21110590","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T02:20:37Z","timestamp":1699928437000},"page":"590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mouse N2a Neuroblastoma Assay: Uncertainties and Comparison with Alternative Cell-Based Assays for Ciguatoxin Detection"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2960-4233","authenticated-orcid":false,"given":"Sandra","family":"Raposo-Garcia","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6134-1373","authenticated-orcid":false,"given":"Alejandro","family":"Cao","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-9076","authenticated-orcid":false,"given":"Celia","family":"Costas","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-0637","authenticated-orcid":false,"given":"M. Carmen","family":"Louzao","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6055-6359","authenticated-orcid":false,"given":"Natalia","family":"Vilari\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9842-6223","authenticated-orcid":false,"given":"Carmen","family":"Vale","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2153-6608","authenticated-orcid":false,"given":"Luis M.","family":"Botana","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3390\/md403082","article-title":"Ciguatoxins: Cyclic polyether modulators of voltage-gated Iion channel function","volume":"4","author":"Nicholson","year":"2006","journal-title":"Mar. Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1021\/tx500503d","article-title":"Synthetic ciguatoxin CTX 3C induces a rapid imbalance in neuronal excitability","volume":"28","author":"Martin","year":"2015","journal-title":"Chem. Res. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1021\/tx500506q","article-title":"Chronic ciguatoxin treatment induces synaptic scaling through voltage gated sodium channels in cortical neurons","volume":"28","author":"Martin","year":"2015","journal-title":"Chem. Res. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"112812","DOI":"10.1016\/j.fct.2022.112812","article-title":"Determination of the toxicity equivalency factors for ciguatoxins using human sodium channels","volume":"160","author":"Louzao","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"849857","DOI":"10.3389\/fmars.2022.849857","article-title":"Food Safety Risk in Germany From Mislabeled Imported Fish: Ciguatera Outbreak Trace-Back, Toxin Elucidation, and Public Health Implications","volume":"9","author":"Loeffler","year":"2022","journal-title":"Front. Mar. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"EFSA (2010). Scientific Opinion on marine biotoxins in shellfish\u2013Emerging toxins: Ciguatoxin group. EFSA J., 8, 1627.","DOI":"10.2903\/j.efsa.2010.1627"},{"key":"ref_7","unstructured":"WHO (2020). Report of the Expert Meeting on Ciguatera Poisoning: Rome, 19\u201323 November 2018, Food and Agriculture Organization."},{"key":"ref_8","unstructured":"FDA (2020). Fish and Fishery Products Hazards and Control Guidance, University of Florida. [4th ed.]."},{"key":"ref_9","first-page":"641","article-title":"In silico simulations and functional cell studies evidence similar potency and distinct binding of Pacific and Caribbean ciguatoxins","volume":"15","author":"Castro","year":"2022","journal-title":"Expo. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1080\/19440049.2012.660707","article-title":"Towards the standardisation of the neuroblastoma (neuro-2a) cell-based assay for ciguatoxin-like toxicity detection in fish: Application to fish caught in the Canary Islands","volume":"29","author":"Caillaud","year":"2012","journal-title":"Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-1-61779-080-5_20","article-title":"Cell sensitivity assays: The MTT assay","volume":"731","author":"Kaspers","year":"2011","journal-title":"Cancer Cell Cult."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Viallon, J., Chinain, M., and Darius, H.T. (2020). Revisiting the Neuroblastoma Cell-Based Assay (CBA-N2a) for the Improved Detection of Marine Toxins Active on Voltage Gated Sodium Channels (VGSCs). Toxins, 12.","DOI":"10.3390\/toxins12050281"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pasinszki, T., Lako, J., and Dennis, T.E. (2020). Advances in Detecting Ciguatoxins in Fish. Toxins, 12.","DOI":"10.3390\/toxins12080494"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1093\/jaoacint\/qsab052","article-title":"Development and Validation of an LC-MS\/MS Method for the Ultra-Trace Analysis of Pacific Ciguatoxins in Fish","volume":"104","author":"Nagae","year":"2021","journal-title":"J. AOAC Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7608","DOI":"10.1021\/ja034990a","article-title":"Synthesis-based approach toward direct sandwich immunoassay for ciguatoxin CTX3C","volume":"125","author":"Oguri","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.chroma.2018.08.008","article-title":"Detection of pacific ciguatoxins using liquid chromatography coupled to either low or high resolution mass spectrometry (LC-MS\/MS)","volume":"1571","author":"Sibat","year":"2018","journal-title":"J. Chromatogr. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.aca.2015.06.018","article-title":"Ultrasensitive and accelerated detection of ciguatoxin by capillary electrophoresis via on-line sandwich immunoassay with rotating magnetic field and nanoparticles signal enhancement","volume":"888","author":"Zhang","year":"2015","journal-title":"Anal. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.toxicon.2005.03.014","article-title":"Biomonitoring of ciguatoxin exposure in mice using blood collection cards","volume":"46","author":"Wang","year":"2005","journal-title":"Toxicon"},{"key":"ref_19","first-page":"625","article-title":"The mouse ciguatoxin bioassay: Directions for use to control fish for consumption","volume":"34","author":"Vernoux","year":"1994","journal-title":"Mem. Qld. Museum. Brisb."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0041-0101(96)00191-2","article-title":"Isolation and characterisation of Caribbean ciguatoxins from the horse-eye jack (Caranx latus)","volume":"35","author":"Vernoux","year":"1997","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1007\/s00204-022-03315-0","article-title":"In vivo subchronic effects of ciguatoxin-related compounds, reevaluation of their toxicity","volume":"96","author":"Camina","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0041-0101(88)90171-7","article-title":"A tissue culture assay for tetrodotoxin, saxitoxin and related toxins","volume":"26","author":"Kogure","year":"1988","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.etap.2017.04.003","article-title":"Human neuronal cell based assay: A new in vitro model for toxicity evaluation of ciguatoxin","volume":"52","author":"Coccini","year":"2017","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101994","DOI":"10.1016\/j.hal.2021.101994","article-title":"Improving in vitro ciguatoxin and brevetoxin detection: Selecting neuroblastoma (Neuro-2a) cells with lower sensitivity to ouabain and veratridine (OV-LS)","volume":"103","author":"Loeffler","year":"2021","journal-title":"Harmful Algae"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1021\/tx0342262","article-title":"Detection of sodium channel activators by a rapid fluorimetric microplate assay","volume":"17","author":"Louzao","year":"2004","journal-title":"Chem. Res. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tudo, A., Rambla-Alegre, M., Flores, C., Sagrista, N., Aguayo, P., Reverte, L., Campas, M., Gouveia, N., Santos, C., and Andree, K.B. (2022). Identification of New CTX Analogues in Fish from the Madeira and Selvagens Archipelagos by Neuro-2a CBA and LC-HRMS. Mar. Drugs, 20.","DOI":"10.3390\/md20040236"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hardison, D.R., Holland, W.C., Darius, H.T., Chinain, M., Tester, P.A., Shea, D., Bogdanoff, A.K., Morris, J.A., Flores Quintana, H.A., and Loeffler, C.R. (2018). Investigation of ciguatoxins in invasive lionfish from the greater caribbean region: Implications for fishery development. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198358"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hardison, D.R., Holland, W.C., McCall, J.R., Bourdelais, A.J., Baden, D.G., Darius, H.T., Chinain, M., Tester, P.A., Shea, D., and Quintana, H.A. (2016). Fluorescent Receptor Binding Assay for Detecting Ciguatoxins in Fish. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153348"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.hal.2017.02.005","article-title":"Toxicity screening of 13 Gambierdiscus strains using neuro-2a and erythrocyte lysis bioassays","volume":"63","author":"Pisapia","year":"2017","journal-title":"Harmful Algae"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.marpolbul.2010.06.017","article-title":"Detection of ciguatoxin-like and paralysing toxins in Trichodesmium spp. from New Caledonia lagoon","volume":"61","author":"Kerbrat","year":"2010","journal-title":"Mar. Pollut. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.toxicon.2008.06.028","article-title":"Comparative study of the use of neuroblastoma cells (Neuro-2a) and neuroblastoma\u00d7 glioma hybrid cells (NG108-15) for the toxic effect quantification of marine toxins","volume":"52","year":"2008","journal-title":"Toxicon"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Castro, D., Manger, R., Vilarino, O., and Gago-Martinez, A. (2020). Evaluation of Matrix Issues in the Applicability of the Neuro-2a Cell Based Assay on the Detection of CTX in Fish Samples. Toxins, 12.","DOI":"10.3390\/toxins12050308"},{"key":"ref_33","unstructured":"Abdullaeva, O.S. (2019). Activation of Voltage-Gated Ion Channels in Neuroblastoma Cells by an Organic Artificial Photoreceptor. [Ph.D. Thesis, Universit\u00e4t Oldenburg]."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41420-018-0078-x","article-title":"Cellular and molecular responses to acute cocaine treatment in neuronal-like N2a cells: Potential mechanism for its resistance in cell death","volume":"4","author":"Badisa","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_35","first-page":"297","article-title":"Vitex negundo induces an anticonvulsant effect by inhibiting voltage gated sodium channels in murine Neuro 2A cell line","volume":"31","author":"Khan","year":"2018","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0304-3940(97)00495-3","article-title":"Regulation of stimulatory adenylyl cyclase signaling during forskolin-induced differentiation of mouse neuroblastoma x rat glioma (NG108-15) cells","volume":"230","author":"Ammer","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1113\/expphysiol.1990.sp003466","article-title":"Forskolin but not isoprenaline increases sodium current from frog cardiac myocytes","volume":"75","author":"Bonvallet","year":"1990","journal-title":"Exp. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1006\/bbrc.2001.4570","article-title":"In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP","volume":"282","author":"Deng","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1113\/jphysiol.1996.sp021604","article-title":"PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade","volume":"495","author":"England","year":"1996","journal-title":"J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1469-7793.1999.0433v.x","article-title":"cAMP-dependent phosphorylation of the tetrodotoxin-resistant voltage-dependent sodium channel SNS","volume":"516","author":"Fitzgerald","year":"1999","journal-title":"J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1038\/s41598-019-39544-0","article-title":"Forskolin and IBMX Induce Neural Transdifferentiation of MSCs Through Downregulation of the NRSF","volume":"9","author":"Thompson","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1111\/j.1471-4159.1988.tb01162.x","article-title":"Comparison of the effects of forskolin and dibutyryl cyclic AMP in neuroblastoma cells: Evidence that some of the actions of dibutyryl cyclic AMP are mediated by butyrate","volume":"51","author":"Yusta","year":"1988","journal-title":"J. Neurochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s001250050780","article-title":"From receptor to transporter: Insulin signalling to glucose transport","volume":"40","author":"Holman","year":"1997","journal-title":"Diabetologia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14611","DOI":"10.1074\/jbc.270.24.14611","article-title":"Regulation of RCK1 currents with a cAMP analog via enhanced protein synthesis and direct channel phosphorylation","volume":"270","author":"Levin","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0076-6879(83)98138-7","article-title":"Perturbation of the structure and function of the Golgi complex by monovalent carboxylic ionophores","volume":"98","author":"Tartakoff","year":"1983","journal-title":"Methods Enzymol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1161\/01.RES.87.1.33","article-title":"Activation of protein kinase A modulates trafficking of the human cardiac sodium channel in Xenopus oocytes","volume":"87","author":"Zhou","year":"2000","journal-title":"Circ. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/B978-0-12-394305-7.00002-1","article-title":"New insights into the regulation of Na+, K+-ATPase by ouabain","volume":"294","author":"Silva","year":"2012","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Castro, D., Est\u00e9vez, P., Leao-Martins, J.M., Dickey, R.W., Garc\u00eda-\u00c1lvarez, N., Real, F., Costa, P.R., and Gago-Mart\u00ednez, A. (2022). Preparation of ciguatoxin reference materials from Canary Islands (Spain) and Madeira Archipelago (Portugal) fish. J. Mar. Sci. Eng., 10.","DOI":"10.3390\/jmse10060835"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107161","DOI":"10.1016\/j.toxicon.2023.107161","article-title":"Evaluation of relative potency of calibrated ciguatoxin congeners by near-infrared fluorescent receptor binding and neuroblastoma cell-based assays","volume":"230","author":"Yokozeki","year":"2023","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.hal.2011.10.009","article-title":"Proteomic analysis of hepatic tissue of ciguatoxin (CTX) contaminated coral reef fish Cephalopholis argus and moray eel Gymnothorax undulatus","volume":"13","author":"Jiang","year":"2012","journal-title":"Harmful Algae"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcmd.2005.10.007","article-title":"Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins","volume":"36","author":"Sauviat","year":"2006","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1242\/jcs.112.23.4223","article-title":"Relationship between Na(+),K(+)-ATPase and cell attachment","volume":"112","author":"Contreras","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.3389\/fphys.2020.01060","article-title":"Ouabain-induced cell death and survival. Role of \u03b11-Na, K-ATPase-mediated signaling and [Na+]i\/[K+]i-dependent gene expression","volume":"11","author":"Lopina","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1248\/bpb.30.247","article-title":"Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells","volume":"30","author":"Qiu","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00380-011-0219-0","article-title":"Effect of ouabain on myocardial ultrastructure and cytoskeleton during the development of ventricular hypertrophy","volume":"28","author":"Zhao","year":"2013","journal-title":"Heart Vessel."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1152\/jn.1996.76.6.3920","article-title":"Functional changes in sodium conductances in the human neuroblastoma cell line SH-SY5Y during in vitro differentiation","volume":"76","author":"Toselli","year":"1996","journal-title":"J. Neurophysiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"42810","DOI":"10.1038\/srep42810","article-title":"Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1","volume":"7","author":"Inserra","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7597","DOI":"10.1074\/jbc.M806481200","article-title":"Synthetic ciguatoxins selectively activate Nav1.8-derived chimeric sodium channels expressed in HEK293 cells","volume":"284","author":"Yamaoka","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1021\/acs.chemrestox.6b00020","article-title":"Toxicological Perspective on Climate Change: Aquatic Toxins","volume":"29","author":"Botana","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1615\/CritRevNeurobiol.v17.i1.20","article-title":"On the use of neuro-2a neuroblastoma cells versus intact neurons in primary culture for neurotoxicity studies","volume":"17","author":"LePage","year":"2005","journal-title":"Crit. Rev. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.toxicon.2005.04.006","article-title":"Use of two detection methods to discriminate ciguatoxins from brevetoxins: Application to great barracuda from Florida Keys","volume":"46","author":"Dechraoui","year":"2005","journal-title":"Toxicon"},{"key":"ref_62","unstructured":"Manger, R.L., Leja, L.S., Lee, S.Y., Hungerford, J.M., and Wekell, M.M. (1999). Cell Bioassay of Neurotoxins. (US5858687A)."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jenvrad.2018.06.019","article-title":"A radioligand receptor binding assay for ciguatoxin monitoring in environmental samples: Method development and determination of quality control criteria","volume":"192","author":"Clausing","year":"2018","journal-title":"J. Environ. Radioact."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/S0169-328X(02)00188-2","article-title":"Molecular cloning, distribution and functional analysis of the NA(V)1.6. Voltage-gated sodium channel from human brain","volume":"103","author":"Burbidge","year":"2002","journal-title":"Brain Res. Mol. Brain Res."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/11\/590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:22:27Z","timestamp":1760131347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/11\/590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,13]]},"references-count":65,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["md21110590"],"URL":"https:\/\/doi.org\/10.3390\/md21110590","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,13]]}}}