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Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and\/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis. Furthermore, applications of FGF2 and\/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.<\/jats:p>","DOI":"10.3390\/ijms24032159","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T02:27:45Z","timestamp":1674440865000},"page":"2159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation"],"prefix":"10.3390","volume":"24","author":[{"given":"Lina Mariana","family":"Tovar","sequence":"first","affiliation":[{"name":"Laboratory of Physiology and Pharmacology for Neural Development, LAND, Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-8589","authenticated-orcid":false,"given":"Carlos Felipe","family":"Burgos","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo E.","family":"Y\u00e9venes","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0260-8744","authenticated-orcid":false,"given":"Gustavo","family":"Moraga-Cid","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Fuentealba","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Coddou","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad Cat\u00f3lica del Norte, Coquimbo 1781421, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bascunan-Godoy","sequence":"additional","affiliation":[{"name":"Departamento de Bot\u00e1nica, Facultad de Ciencias Naturales y Oceanogr\u00e1ficas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-7873","authenticated-orcid":false,"given":"Claudio","family":"Catrupay","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology for Neural Development, LAND, Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Torres","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology for Neural Development, LAND, Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8131-3265","authenticated-orcid":false,"given":"Patricio A.","family":"Castro","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Pharmacology for Neural Development, LAND, Departamento de Fisiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1146\/annurev-genet-120213-092208","article-title":"Genetic, epigenetic, and environmental contributions to neural tube closure","volume":"48","author":"Wilde","year":"2014","journal-title":"Annu. 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