{"id":14440,"date":"2024-05-23T07:43:55","date_gmt":"2024-05-23T07:43:55","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=14440"},"modified":"2024-05-23T07:43:55","modified_gmt":"2024-05-23T07:43:55","slug":"2024-single-cell-ionic-current-phenotyping-elucidates-non-canonical-features-and-predictive-potential-of-cardiomyocytes-during-automated-drug-experiments","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-single-cell-ionic-current-phenotyping-elucidates-non-canonical-features-and-predictive-potential-of-cardiomyocytes-during-automated-drug-experiments\/","title":{"rendered":"2024 &#8211; Single-cell ionic current phenotyping elucidates non-canonical features and predictive potential of cardiomyocytes during automated drug experiments"},"content":{"rendered":"<p>All new drugs must go through preclinical screening tests to determine their proarrhythmic potential. While these assays effectively filter out dangerous drugs, they are too<br \/>\nconservative, often misclassifying safe compounds as proarrhythmic. In this study, we attempt to address this shortcoming with a novel, medium-throughput drug-screening approach: we use an automated patch-clamp system to acquire optimized voltage clamp (VC) and action potential (AP) data from human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) at several drug concentrations (baseline, 3\u00d7, 10\u00d7 and 20\u00d7 the effective free plasma concentrations). With our novel method, we show correlations between I<sub>Na<\/sub> block and upstroke slowing after treatment with flecainide or quinine. Additionally, after quinine treatment, we identify significant reductions in current during voltage steps designed to isolate I<sub>f<\/sub> and I<sub>Ks<\/sub>. However, we do not detect any I<sub>Kr<\/sub> block by either drug, and upon further investigation, do not see any I<sub>Kr<\/sub> present in the iPSC-CMs when prepared for automated patch experiments (i.e. in suspension) \u2013 this is in contrast to similar experiments we have conducted with these cells using the manual patch setup. In this study, we: (1) present a proof-of-concept demonstration of a single-cell medium-throughput drug study, and (2) characterize the non-canonical electrophysiology of iPSC-CMs when prepared for experiments in a medium-throughput setting.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50,53,77],"therapeutic_areas":[143],"target_categories":[61],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-14440","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","application_areas-cell-ipscs-profiling","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/14440","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=14440"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=14440"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=14440"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=14440"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=14440"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=14440"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=14440"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=14440"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=14440"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}