{"id":6197,"date":"2023-02-17T06:56:39","date_gmt":"2023-02-17T06:56:39","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2017-l-type-calcium-channel-inhibition-contributes-to-the-proarrhythmic-effects-of-aconitine-in-human-cardiomyocytes\/"},"modified":"2023-02-17T06:56:40","modified_gmt":"2023-02-17T06:56:40","slug":"2017-l-type-calcium-channel-inhibition-contributes-to-the-proarrhythmic-effects-of-aconitine-in-human-cardiomyocytes","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2017-l-type-calcium-channel-inhibition-contributes-to-the-proarrhythmic-effects-of-aconitine-in-human-cardiomyocytes\/","title":{"rendered":"2017 &#8211; L-Type Calcium Channel Inhibition Contributes to the Proarrhythmic Effects of Aconitine in Human Cardiomyocytes"},"content":{"rendered":"<p>Aconitine (ACO) is well-known for causing lethal ventricular tachyarrhythmias. While cardiac Na<sup>+<\/sup>\u00a0channel opening during repolarization has long been documented in animal cardiac myocytes, the cellular effects and mechanism of ACO in human remain unexplored. This study aimed to assess the proarrhythmic effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). ACO concentration-dependently (0.3 ~ 3.0 \u03bcM) shortened the action potentials (AP) durations (APD) in ventricular-like hiPSC-CMs by > 40% and induced delayed after-depolarization. Laser-scanning confocal calcium imaging analysis showed that ACO decreased the duration and amplitude of [Ca<sup>2+<\/sup>]i\u00a0transients and increased in the beating frequencies by over 60%. Moreover, ACO was found to markedly reduce the L-type calcium channel (LTCC) currents (ICa,L) in hiPSC-CMs associated with a positive-shift of activation and a negative shift of inactivation. ACO failed to alter the peak and late Na<sup>+<\/sup>\u00a0currents (INa) in hiPSC-CMs while it drastically increased the late INa\u00a0in Guinea-pig ventricular myocytes associated with enhanced activation\/delayed inactivation of INa\u00a0at -55 mV~ -85 mV. Further, the effects of ACO on ICa,L, INa\u00a0and the rapid delayed rectifier potassium current (I<sup>Kr<\/sup>) were validated in heterologous expression systems by automated voltage-clamping assays and a moderate suppression of I<sup>Kr<\/sup>\u00a0was observed in addition to concentration-dependent ICa,L\u00a0inhibition. Lastly, increased beating frequency, decreased Ca<sup>2+<\/sup>\u00a0wave and shortened field potential duration were recorded from hiPSC-CMs by microelectrode arrays assay. In summary, our data demonstrated that LTCC inhibition could play a main role in the proarrhythmic action of ACO in human cardiomyocytes.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[54],"target_categories":[61],"target_families":[332,340,346],"targets":[91,93,96],"resource_keyword":[],"class_list":["post-6197","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","therapeutic_areas-cardiac-safety-cipa","target_categories-voltage-gated-ion-channels","target_families-nav-channels","target_families-cav-channels","target_families-inwardly-rectifying-potassium-channels-kir","targets-cav1-2","targets-nav1-5","targets-kir2-1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6197","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=6197"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6197"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6197"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6197"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6197"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6197"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6197"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6197"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6197"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}