{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:38:28Z","timestamp":1790811508893,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-15-CE14-0004-02"],"award-info":[{"award-number":["ANR-15-CE14-0004-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-11-LABX-0015"],"award-info":[{"award-number":["ANR-11-LABX-0015"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013414","name":"R\u00e9gion Pays de la Loire","doi-asserted-by":"publisher","award":["2016-11092\/11093"],"award-info":[{"award-number":["2016-11092\/11093"]}],"id":[{"id":"10.13039\/501100013414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>IKr current, a major component of cardiac repolarization, is mediated by human Ether-\u00e0-go-go-Related Gene (hERG, Kv11.1) potassium channels. The blockage of these channels by pharmacological compounds is associated to drug-induced long QT syndrome (LQTS), which is a life-threatening disorder characterized by ventricular arrhythmias and defects in cardiac repolarization that can be illustrated using cardiomyocytes derived from human-induced pluripotent stem cells (hiPS-CMs). This study was meant to assess the modification in hiPS-CMs excitability and contractile properties by BeKm-1, a natural scorpion venom peptide that selectively interacts with the extracellular face of hERG, by opposition to reference compounds that act onto the intracellular face. Using an automated patch-clamp system, we compared the affinity of BeKm-1 for hERG channels with some reference compounds. We fully assessed its effects on the electrophysiological, calcium handling, and beating properties of hiPS-CMs. By delaying cardiomyocyte repolarization, the peptide induces early afterdepolarizations and reduces spontaneous action potentials, calcium transients, and contraction frequencies, therefore recapitulating several of the critical phenotype features associated with arrhythmic risk in drug-induced LQTS. BeKm-1 exemplifies an interesting reference compound in the integrated hiPS-CMs cell model for all drugs that may block the hERG channel from the outer face. Being a peptide that is easily modifiable, it will serve as an ideal molecular platform for the design of new hERG modulators displaying additional functionalities.<\/jats:p>","DOI":"10.3390\/ijms21197167","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T10:39:58Z","timestamp":1601289598000},"page":"7167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Functional Impact of BeKm-1, a High-Affinity hERG Blocker, on Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells"],"prefix":"10.3390","volume":"21","author":[{"given":"Stephan","family":"De Waard","sequence":"first","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"},{"name":"LabEx Ion Channels, Science &amp; Therapeutics, F-06560 Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Montnach","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2269-5750","authenticated-orcid":false,"given":"Barbara","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Nicolas","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-5232","authenticated-orcid":false,"given":"Virginie","family":"Forest","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-0998","authenticated-orcid":false,"given":"Flavien","family":"Charpentier","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Elia","family":"Mangoni","sequence":"additional","affiliation":[{"name":"LabEx Ion Channels, Science &amp; Therapeutics, F-06560 Valbonne, France"},{"name":"Institut de G\u00e9nomique Fonctionnelle, CNRS, INSERM, Universit\u00e9 de Montpellier, F34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gaborit","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Ronjat","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"},{"name":"LabEx Ion Channels, Science &amp; Therapeutics, F-06560 Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gildas","family":"Loussouarn","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5330-2008","authenticated-orcid":false,"given":"Patricia","family":"Lemarchand","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9615","authenticated-orcid":false,"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[{"name":"L\u2019institut du thorax, INSERM, CNRS, Universit\u00e9 de Nantes, F-44007 Nantes, France"},{"name":"LabEx Ion Channels, Science &amp; Therapeutics, F-06560 Valbonne, France"},{"name":"Smartox Biotechnology, 6 rue des Platanes, F-38120 Saint-Egr\u00e8ve, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9868","DOI":"10.1074\/jbc.M005973200","article-title":"An ERG channel inhibitor from the scorpion Buthus eupeus","volume":"276","author":"Korolkova","year":"2001","journal-title":"J. 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