{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:15:09Z","timestamp":1792718109617,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Recent evidence demonstrated that alterations in the QT interval duration on the ECG are not only determined by mutations in genes for ion channels, but also by modulators of ion channels. Changes in the QT interval duration beyond certain thresholds are pathological and can lead to sudden cardiac death. We here focus on the ion channel modulator nitric oxide synthase 1 adaptor protein (Nos1ap). Whole\u2010cell patch\u2010clamp measurements of a conditional transgenic mouse model exhibiting cardiac\u2010specific Nos1ap over\u2010expression revealed a Nos1ap\u2010dependent increase of L\u2010type calcium channel nitrosylation, which led to increased susceptibility to ventricular tachycardias associated with a decrease in QT duration and shortening of APD<jats:sub>90<\/jats:sub> duration. Survival was significantly reduced (60% after 12\u2009weeks vs. 100% in controls). Examination of the structural features of the hearts of transgenic mice revealed constant heart dimensions and wall thickness without abnormal fibrosis content or BNP production after 3\u2009months of Nos1ap over\u2010expression compared to controls. Nos1ap over\u2010expression did not alter cGMP production or ROS concentration. Our study showed that myocardial over\u2010expression of Nos1ap leads to the shortening of the QT interval and reduces the survival rate of transgenic animals, perhaps via the development of ventricular arrhythmias. We conclude that Nos1ap overexpression causes targeted subcellular localization of Nos1 to the CaV1.2 with a subsequent decrease of ADP<jats:sub>90<\/jats:sub> and the QT interval. This causes detrimental cardiac arrhythmias in transgenic mice.<\/jats:p>","DOI":"10.1002\/2211-5463.13520","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T04:11:15Z","timestamp":1668053475000},"page":"118-132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inducible over\u2010expression of cardiac Nos1ap causes short <scp>QT<\/scp> syndrome in transgenic mice"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-2089","authenticated-orcid":false,"given":"Monique","family":"J\u00e4nsch","sequence":"first","affiliation":[{"name":"Department of Cardiology, Nephrology and Pneumology, Brandenburg Medical School University Hospital Brandenburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubomir T.","family":"Lubomirov","sequence":"additional","affiliation":[{"name":"Institute of Physiology Brandenburg Medical School Theodor Fontane  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Trum","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital Regensburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Williams","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center and Department of Internal Medicine I University Hospital W\u00fcrzburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology Heinrich Heine University  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Schuh","sequence":"additional","affiliation":[{"name":"Institute of Physiology University of W\u00fcrzburg  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