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Experiments were conducted using frog myelinated nerve fibers as a model system. Application of EqtII led to an approximately two-fold increase in the nodal volume of myelinated axons, but only when extracellular Ca2+ was present. Replacing extracellular Cl\u2212 with isethionate had no measurable effect on this response, whereas substitution of NaCl with either sucrose or LiCl, an established Na+\/Ca2+ exchanger (NCX) inhibitor, abolished the swelling. The persistence of the effect in the presence of tetrodotoxin indicates that voltage-gated Na+ channels are not involved in the underlying mechanism. Our data suggest that Ca2+ influx through EqtII-induced membrane pores raises intracellular Ca2+ levels, thereby stimulating the NCX in its forward-operating mode. This process promotes Ca2+ extrusion in exchange for Na+ entry. The resulting accumulation of intracellular Na+ increases osmotic pressure within the axon, leading to water influx and nodal swelling.<\/jats:p>","DOI":"10.3390\/md24050187","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:53:24Z","timestamp":1779371604000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Equinatoxin II: How a Cationic Pore-Forming Sea Anemone Toxin Drives Nodal Swelling of Myelinated Nerve Fibers"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-0888","authenticated-orcid":false,"given":"Evelyne","family":"Benoit","sequence":"first","affiliation":[{"name":"Service d\u2019Ing\u00e9nierie Mol\u00e9culaire Pour la Sant\u00e9 (SIMoS), EMR CNRS 9004, D\u00e9partement M\u00e9dicaments et Technologies Pour la Sant\u00e9 (DMTS), Institut des Sciences du Vivant Fr\u00e9d\u00e9ric Joliot, Commissariat \u00e0 l\u2019\u00e9nergie atomique et aux \u00e9nergies alternatives (CEA), Universit\u00e9 Paris-Saclay, F-91191 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0636-9277","authenticated-orcid":false,"given":"Robert","family":"Frange\u017e","sequence":"additional","affiliation":[{"name":"Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbi\u010deva 60, S-1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Ouanounou","sequence":"additional","affiliation":[{"name":"UMR CNRS 9197, Institut des Neurosciences Paris-Saclay (NeuroPSI), Universit\u00e9 Paris-Saclay, F-91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6400-1107","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric A.","family":"Meunier","sequence":"additional","affiliation":[{"name":"Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, School of Biomedical Sciences, The University of Queensland, St Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-7267","authenticated-orcid":false,"given":"Dusan","family":"\u0160uput","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, S-1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-8994","authenticated-orcid":false,"given":"Jordi","family":"Molg\u00f3","sequence":"additional","affiliation":[{"name":"Service d\u2019Ing\u00e9nierie Mol\u00e9culaire Pour la Sant\u00e9 (SIMoS), EMR CNRS 9004, D\u00e9partement M\u00e9dicaments et Technologies Pour la Sant\u00e9 (DMTS), Institut des Sciences du Vivant Fr\u00e9d\u00e9ric Joliot, Commissariat \u00e0 l\u2019\u00e9nergie atomique et aux \u00e9nergies alternatives (CEA), Universit\u00e9 Paris-Saclay, F-91191 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.3390\/md10081812","article-title":"Sea anemone (Cnidaria, Anthozoa, Actiniaria) toxins: An overview","volume":"10","author":"Frazao","year":"2012","journal-title":"Mar. 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