{"id":6699,"date":"2023-02-17T07:17:45","date_gmt":"2023-02-17T07:17:45","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/nav1-5-nav1-5-%ce%b4kpq-late-ina-current-properties-and-pharmacology-on-the-syncropatch-384i\/"},"modified":"2023-02-17T07:17:45","modified_gmt":"2023-02-17T07:17:45","slug":"nav1-5-nav1-5-%ce%b4kpq-late-ina-current-properties-and-pharmacology-on-the-syncropatch-384i","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/nav1-5-nav1-5-%ce%b4kpq-late-ina-current-properties-and-pharmacology-on-the-syncropatch-384i\/","title":{"rendered":"NaV1.5 &#8211; &#8220;NaV1.5-\u0394KPQ late INa current properties and pharmacology on the SyncroPatch 384i&#8221;"},"content":{"rendered":"<p>The cardiac late Na current (late INa) generates persistent currents throughout the plateau phase of the cardiac action potential. Several mutations in the SCN5A gene cause a form of hereditary long QT syndrome (LQT3)1-3. The \u0394KPQ mutation deletes residues Lys 1505, Pro 1506 and Gln 1507, resulting in a sustained, non-inactivating current during long (over 50 ms) depolarizations1,2. This sustained current causes prolongation of the action potential which can result in fatal ventricular arrhythmias such as Torsade de Pointes (TdP)1.One aim of the Comprehensive\u00a0In Vitro\u00a0Pro-arrhythmia Assay (CiPA) initiative is to improve drug safety testing in pre-clinical development by evaluating the pro-arrhythmic risk of a compound4,5. Validation studies confirm that testing the effect of compounds on an increased number of human cardiac ion channel currents including INa\u00a0(NaV1.5 peak and late current) as well as I<sup>Kr<\/sup>\u00a0(hERG) leads to improved prediction of their clinical risk. Late INa\u00a0can be recorded in WT NaV1.5 channels using the toxin ATX-II or veratridine, or using a cell line with LQT3 mutations in NaV1.5 without the need for pharmacological enhancement. The latter might also reduce the risk of cross-reactions between late-current enhancers and test compounds.Here we present data collected on the Syncro- Patch 384i showing the peak and late INa\u00a0current re\u00accorded from WT and NaV1.5-\u0394KPQ cell lines. Peak current could be reliably recorded from both cell types. In WT cells, late INa was negligible in the absence of ATX-II, whereas the late INa\u00a0from NaV1.5-\u0394KPQ cells could be reliably recorded. Peak current from WT, and peak and late INa\u00a0from NaV1.5-\u0394KPQ was inhibited by ranolazine and mexiletine and IC<sub>50<\/sub>\u00a0values agreed well with the literature6.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[90],"application_areas":[50],"therapeutic_areas":[54],"target_categories":[61],"target_families":[332],"targets":[93],"resource_keyword":[],"class_list":["post-6699","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-application-note","application_areas-ion-channels","therapeutic_areas-cardiac-safety-cipa","target_categories-voltage-gated-ion-channels","target_families-nav-channels","targets-nav1-5"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6699","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=6699"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6699"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6699"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6699"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6699"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6699"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6699"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6699"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6699"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}