Germ layer-specific interaction of ion channels and transporters controls membrane potential and left-right patterning

Germ layer-specific interaction of ion channels and transporters controls membrane potential and left-right patterning | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Germ layer-specific interaction of ion channels and transporters controls membrane potential and left-right patterning Leonid Tyan, Valentyna Kostiuk, Nicholas Diab, David Zenisek, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6515264/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Emerging evidence indicates that ion channels and transporters are critical for normal embryonic development. They are essential for establishing membrane potential (Vm), a property of all cells. However, it is uncertain if embryonic cells have regional differences in electrical behavior that play a role in defining local cell fates. In our study, by manipulating ion concentrations and applying a wide spectrum of inhibitors, we demonstrate that various ion channels and transporters differentially determine Vm in specific germ layers of the embryo. Altering the electrical properties of the embryo leads to localized changes in cell fate and alterations in left-right patterning, which can lead to severe diseases, including heterotaxy and congenital heart disease. Our results indicate that the electrical properties of early embryonic cells are regionally specified and affect local cell fates. Biological sciences/Developmental biology/Embryology Biological sciences/Physiology/Cardiovascular biology Full Text Additional Declarations Yes there is potential Competing Interest. Mustafa K. Khokha is a founder and president of Victory Genomics, Inc. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6515264","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":449819608,"identity":"d7681879-349e-42f0-8630-9a2243ce9a2b","order_by":0,"name":"Leonid Tyan","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Leonid","middleName":"","lastName":"Tyan","suffix":""},{"id":449819609,"identity":"be1827db-1f9a-41c0-913e-fd68e6dd600c","order_by":1,"name":"Valentyna Kostiuk","email":"","orcid":"https://orcid.org/0000-0003-3405-7518","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Valentyna","middleName":"","lastName":"Kostiuk","suffix":""},{"id":449819610,"identity":"a38e755c-4040-45ab-bcb8-0818aa4b94d3","order_by":2,"name":"Nicholas Diab","email":"","orcid":"","institution":"Vanderbilt University","correspondingAuthor":false,"prefix":"","firstName":"Nicholas","middleName":"","lastName":"Diab","suffix":""},{"id":449819607,"identity":"cf148eec-e66e-4ed0-816a-fbd89ffbec17","order_by":3,"name":"David Zenisek","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYDCCA0DEA2IwMzAwNlQwMPCBODzEaznDwMBGjBa4AsbGNiK08B0/Y3jgDUOdnDk7+8OHM+cdlmdjb2B88LYNtxbJMzkGB+cwsBlbNvMYG27cdtiwjecAs+FcPFoMDqQlHOZh4EnccJiHTfLhtsOMbRIJbNK8+LScfwbSIlG/4TD7858P5xy2b5N/wP4br5YbyQeAWgwSDA4zmDFubDic2CbBwMaMT4vkjccHDs4xSDAEOsxYcsax9OQ2nsRmyTnncGvhO5/Y/OFNRZ28wfnjDz/21Fjb9rMfPvjhTRluLVDnwVnNDKAYJaQeBdSRpHoUjIJRMApGBgAAJahU3TFlx0MAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-6052-0348","institution":"Yale University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"David","middleName":"","lastName":"Zenisek","suffix":""},{"id":449819611,"identity":"77c13eb9-a6ab-42f7-9cc8-543165b06ba4","order_by":4,"name":"Mustafa Khokha","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Mustafa","middleName":"","lastName":"Khokha","suffix":""}],"badges":[],"createdAt":"2025-04-23 19:50:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6515264/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6515264/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83939895,"identity":"cf7f9280-f8b3-4f19-8a7a-a4e9c2636a39","added_by":"auto","created_at":"2025-06-04 17:52:31","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1418239,"visible":true,"origin":"","legend":"Article File","description":"","filename":"TyanregionalionchannelsfinalNC.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6515264/v1_covered_1c03ef88-9aeb-4f23-97c6-5998988e317c.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nMustafa K. 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