{"id":13638,"date":"2024-02-08T09:24:11","date_gmt":"2024-02-08T09:24:11","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=13638"},"modified":"2024-02-08T09:24:11","modified_gmt":"2024-02-08T09:24:11","slug":"2024-cellular-level-analyses-of-scn5a-mutations-in-left-ventricular-noncompaction-cardiomyopathy-suggest-electrophysiological-mechanisms-for-ventricular-tachycardia","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2024-cellular-level-analyses-of-scn5a-mutations-in-left-ventricular-noncompaction-cardiomyopathy-suggest-electrophysiological-mechanisms-for-ventricular-tachycardia\/","title":{"rendered":"2024 &#8211; Cellular-level analyses of SCN5A mutations in left ventricular noncompaction cardiomyopathy suggest electrophysiological mechanisms for ventricular tachycardia"},"content":{"rendered":"<p>Left ventricular noncompaction cardiomyopathy (LVNC) is a cardiovascular disease characterized by arrhythmia and heart failure. In this study, LVNC myocardial samples were collected from patients who underwent heart transplantation and were analyzed using exome sequencing. Approximately half of the LVNC patients carried\u00a0<em>SCN5A<\/em>\u00a0variants, which are associated with clinical symptoms of\u00a0ventricular tachycardia. To investigate the electrophysiological functions of these\u00a0<em>SCN5A<\/em>\u00a0variants and the underlying mechanism by which they increase arrhythmia susceptibility in LVNC patients, functional evaluations were conducted in CHO\u2013K1 cells and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using patch-clamp or\u00a0microelectrode\u00a0array (MEA) techniques. These findings demonstrated that these\u00a0<em>SCN5A<\/em>\u00a0mutants exhibited gain-of-function properties, leading to increased channel activation and enhanced fast inactivation in CHO\u2013K1 cells. Additionally, these mutants enhanced the excitability and\u00a0contractility\u00a0of the cardiomyocyte population in hESC-CMs models. All\u00a0<em>SCN5A<\/em>\u00a0variants induced fibrillation-like arrhythmia and increased the heart rate in cardiomyocytes. However, the administration of Lidocaine, an antiarrhythmic drug that acts on sodium ion channels, was able to rescue or alleviate fibrillation-like arrhythmias and secondary beat phenomenon. Based on these findings, it is speculated that\u00a0<em>SCN5A<\/em>\u00a0variants may contribute to susceptibility to arrhythmia in LVNC patients. Furthermore, the construction of cardiomyocyte models with\u00a0<em>SCN5A<\/em>\u00a0variants and their application in drug screening may facilitate the development of precise therapies for arrhythmia in the future.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[53,77],"therapeutic_areas":[143],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-13638","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-assay-development-and-validation","application_areas-cell-ipscs-profiling","therapeutic_areas-assay-development-and-validation"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/13638","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=13638"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=13638"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=13638"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=13638"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=13638"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=13638"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=13638"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=13638"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=13638"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}