{"id":14736,"date":"2024-07-01T09:53:16","date_gmt":"2024-07-01T09:53:16","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=14736"},"modified":"2025-04-09T17:31:54","modified_gmt":"2025-04-09T17:31:54","slug":"2024-transient-titin-dependent-ventricular-defects-during-development-lead-to-adult-atrial-arrhythmia-and-impaired-contractility","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-transient-titin-dependent-ventricular-defects-during-development-lead-to-adult-atrial-arrhythmia-and-impaired-contractility\/","title":{"rendered":"2024 &#8211; Transient titin-dependent ventricular defects during development lead to adult atrial arrhythmia and impaired contractility"},"content":{"rendered":"<p>Developmental causes of the most common arrhythmia, atrial fibrillation (AF), are poorly defined, with compensation potentially masking arrhythmic risk. Here, we delete 9 amino acids (\u03949) within a conserved domain of the giant protein titin\u2019s A-band in zebrafish and human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs). We find that\u00a0<em>ttna<\/em><sup>\u03949\/\u03949<\/sup>\u00a0zebrafish embryos\u2019 cardiac morphology is perturbed and accompanied by reduced functional output, but ventricular function recovers within days. Despite normal ventricular function,\u00a0<em>ttna<\/em><sup>\u03949\/\u03949<\/sup>\u00a0adults exhibit AF and atrial myopathy, which are recapitulated in\u00a0<em>TTN<\/em><sup>\u03949\/\u03949<\/sup>-hiPSC-aCMs. Additionally, action potential is shortened and slow delayed rectifier potassium current (<em>I<\/em><sub>Ks<\/sub>) is increased due to aberrant atrial natriuretic peptide (ANP) levels. Strikingly, suppression of\u00a0<em>I<\/em><sub>Ks<\/sub>\u00a0in both models prevents AF and improves atrial contractility. Thus, a small internal deletion in titin causes developmental abnormalities that increase the risk of AF via ion channel remodeling, with implications for patients who harbor disease-causing variants in sarcomeric proteins.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,53,77],"therapeutic_areas":[143],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-14736","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","application_areas-cell-ipscs-profiling","therapeutic_areas-assay-development-and-validation"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/14736","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=14736"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=14736"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=14736"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=14736"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=14736"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=14736"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=14736"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=14736"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=14736"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}