{"id":14737,"date":"2024-07-02T08:47:36","date_gmt":"2024-07-02T08:47:36","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=14737"},"modified":"2024-07-02T08:47:36","modified_gmt":"2024-07-02T08:47:36","slug":"2024-chamber-specific-contractile-responses-of-atrial-and-ventricular-hipsc-cardiomyocytes-to-gpcr-and-ion-channel-targeting-compounds-a-microphysiological-system-for-cardiac-drug-development","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2024-chamber-specific-contractile-responses-of-atrial-and-ventricular-hipsc-cardiomyocytes-to-gpcr-and-ion-channel-targeting-compounds-a-microphysiological-system-for-cardiac-drug-development\/","title":{"rendered":"2024 &#8211; Chamber-specific contractile responses of atrial and ventricular hiPSC-cardiomyocytes to GPCR and ion channel targeting compounds: A microphysiological system for cardiac drug development"},"content":{"rendered":"<p id=\"sp0055\">Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) have found utility for conducting\u00a0<em>in vitro<\/em>\u00a0drug screening and disease modelling to gain crucial insights into pharmacology or disease phenotype. However, diseases such as atrial fibrillation, affecting &gt;33\u00a0M people worldwide, demonstrate the need for cardiac subtype-specific cells. Here, we sought to investigate the base characteristics and pharmacological differences between commercially available chamber-specific atrial or ventricular hiPSC-CMs seeded onto ultra-thin, flexible PDMS membranes to simultaneously measure contractility in a 96 multi-well format. We investigated the effects of GPCR agonists (acetylcholine and carbachol), a Ca<sup>2+<\/sup>\u00a0channel agonist (S-Bay K8644), an HCN channel antagonist (ivabradine) and K<sup>+<\/sup>\u00a0channel antagonists (4-AP and vernakalant). We observed differential effects between atrial and ventricular hiPSC-CMs on contractile properties including beat rate, beat duration, contractile force and evidence of arrhythmias at a range of concentrations.<\/p>\n<p id=\"sp0060\">As an excerpt of the compound analysis, S-Bay K8644 treatment showed an induced concentration-dependent transient increase in beat duration of atrial hiPSC-CMs, whereas ventricular cells showed a physiological increase in beat rate over time. Carbachol treatment produced marked effects on atrial cells, such as increased beat duration alongside a decrease in beat rate over time, but only minimal effects on ventricular cardiomyocytes. In the context of this chamber-specific pharmacology, we not only add to contractile characterization of hiPSC-CMs but propose a multi-well platform for medium-throughput early compound screening.<\/p>\n<p id=\"sp0065\">Overall, these insights illustrate the key pharmacological differences between chamber-specific cardiomyocytes and their application on a multi-well contractility platform to gain insights for\u00a0<em>in vitro<\/em>\u00a0cardiac liability studies and disease modelling.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[35],"resource_type":[75],"application_areas":[53,77],"therapeutic_areas":[143],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-14737","resource_library","type-resource_library","status-publish","hentry","products_tags-flexcyte-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\/14737","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=14737"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=14737"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=14737"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=14737"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=14737"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=14737"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=14737"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=14737"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=14737"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}