{"entity": "researcher", "timestamp": "2026-09-28T11:49:22.800Z", "family": "Ottosson", "given": "Nina E", "initials": "NE", "orcid": "0000-0003-2159-6731", "affiliations": ["Department of Clinical and Experimental Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/435eb22b7d194cb5969454cc3e180e9a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/435eb22b7d194cb5969454cc3e180e9a"}}, "publications": [{"entity": "publication", "iuid": "f83205fdb4d747a196b923fb57b84d4f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f83205fdb4d747a196b923fb57b84d4f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f83205fdb4d747a196b923fb57b84d4f"}}, "title": "Rescue of loss-of-function long QT syndrome-associated mutations in KV7.1/KCNE1 by the endocannabinoid N-arachidonoyl-L-serine (ARA-S).", "authors": [{"family": "Hiniesto-I\u00f1igo", "given": "Irene", "initials": "I"}, {"family": "Sridhar", "given": "Akshay", "initials": "A"}, {"family": "Louradour", "given": "Julien", "initials": "J", "orcid": "0000-0002-0649-4975", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74d0214f0da644c0b066ce3c5660c6f0.json"}}, {"family": "De la Cruz", "given": "Alicia", "initials": "A"}, {"family": "Lundholm", "given": "Siri", "initials": "S"}, {"family": "Jauregi-Miguel", "given": "Amaia", "initials": "A"}, {"family": "Giannetti", "given": "Federica", "initials": "F", "orcid": "0000-0002-1785-5529", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0cd9bc80902d4ded924678aa78e9d241.json"}}, {"family": "Sala", "given": "Luca", "initials": "L", "orcid": "0000-0002-4129-6632", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5e6a27d1e973424fa525c1239d2dab29.json"}}, {"family": "Odening", "given": "Katja E", "initials": "KE", "orcid": "0000-0001-6999-841X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/528c0c4fb7e94c54b481e3a19ed684ca.json"}}, {"family": "Larsson", "given": "H Peter", "initials": "HP", "orcid": "0000-0002-1688-2525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74799f68074140fcb62632be58ce0920.json"}}, {"family": "Ottosson", "given": "Nina E", "initials": "NE", "orcid": "0000-0003-2159-6731", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/435eb22b7d194cb5969454cc3e180e9a.json"}}, {"family": "Liin", "given": "Sara I", "initials": "SI", "orcid": "0000-0001-8493-0114", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/236f04e5bac442599389f47248d54c75.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "Br J Pharmacol", "issn": "1476-5381", "volume": "182", "issue": "13", "pages": "2861-2877", "issn-l": null}, "abstract": "Congenital long QT syndrome (LQTS) involves genetic mutations affecting ion channels, leading to a prolonged QT interval and increased risk of potentially lethal ventricular arrhythmias. Mutations in the genes encoding KV7.1/KCNE1 are the most frequent, with channel loss-of-function contributing to LQTS. The endocannabinoid N-arachidonoyl-L-serine (ARA-S) has been shown to facilitate activation of wild type KV7.1/KCNE1 channels and to counteract a prolonged QT interval in isolated guinea pig hearts. In this study, we examine the ability of ARA-S to facilitate activation of LQTS-associated mutations, in various regions of the channel, and hence to counteract loss-of-function.\n\nThe two-electrode voltage clamp technique on Xenopus oocytes expressing human KV7.1/KCNE1 channels was used to investigate the effects of ARA-S in 20 LQTS type 1-associated mutations distributed across the channel. Thereafter, different electrophysiology was used to assess ARA-S effects in mammalian cells.\n\nARA-S enhanced the function of all mutated channels by shifting V50 and increasing current amplitude. However, the magnitude of effect varied, related to whether mutations were in one of the two putative ARA-S binding sites on the channel as suggested by molecular dynamics simulations. ARA-S displayed translational potential by facilitating channel opening in mammalian cells and shortening the action potential duration in cardiomyocytes.\n\nThis study demonstrates the rescuing capability of ARA-S on a diverse set of LQTS mutants. These insights may aid in developing drug compounds using ARA-S sites and mechanisms and guide interpretation of which LQTS mutants respond well to such compounds.", "doi": "10.1111/bph.70008", "pmid": "40083204", "labels": [], "xrefs": [], "notes": [], "created": "2026-09-23T12:32:21.745Z", "modified": "2026-09-23T12:32:22.018Z"}, {"entity": "publication", "iuid": "b0dd278be5de46709e098456c7e0855e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b0dd278be5de46709e098456c7e0855e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b0dd278be5de46709e098456c7e0855e"}}, "title": "A drug pocket at the lipid bilayer-potassium channel interface.", "authors": [{"family": "Ottosson", "given": "Nina E", "initials": "NE", "orcid": "0000-0003-2159-6731", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/435eb22b7d194cb5969454cc3e180e9a.json"}}, {"family": "Silver\u00e5 Ejneby", "given": "Malin", "initials": "M", "orcid": "0000-0002-8151-5430", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad77e0bdda864923a0a4c5d108a4ddd7.json"}}, {"family": "Wu", "given": "Xiongyu", "initials": "X"}, {"family": "Yazdi", "given": "Samira", "initials": "S", "orcid": "0000-0003-2198-4590", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c6d3b64800c44fdbb2211cc5230a42d.json"}}, {"family": "Konradsson", "given": "Peter", "initials": "P"}, {"family": "Lindahl", "given": "Erik", "initials": "E", "orcid": "0000-0002-2734-2794", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9eb30fa60f9b4b95842ac9d9f3a0eaa9.json"}}, {"family": "Elinder", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-9125-5583", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6af26d4c0637492696fb91a3417fe902.json"}}], "type": "journal article", "published": "2017-10-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "3", "issue": "10", "pages": "e1701099", "issn-l": "2375-2548"}, "abstract": "Many pharmaceutical drugs against neurological and cardiovascular disorders exert their therapeutic effects by binding to specific sites on voltage-gated ion channels of neurons or cardiomyocytes. To date, all molecules targeting known ion channel sites bind to protein pockets that are mainly surrounded by water. We describe a lipid-protein drug-binding pocket of a potassium channel. We synthesized and electrophysiologically tested 125 derivatives, analogs, and related compounds to dehydroabietic acid. Functional data in combination with docking and molecular dynamics simulations mapped a binding site for small-molecule compounds at the interface between the lipid bilayer and the transmembrane segments S3 and S4 of the voltage-sensor domain. This fundamentally new binding site for small-molecule compounds paves the way for the design of new types of drugs against diseases caused by altered excitability.", "doi": "10.1126/sciadv.1701099", "pmid": "29075666", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5656419"}, {"db": "pii", "key": "1701099"}], "notes": [], "created": "2018-12-05T12:07:48.359Z", "modified": "2026-09-23T11:46:19.431Z"}]}