{"id":6681,"date":"2023-02-17T07:15:33","date_gmt":"2023-02-17T07:15:33","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2022-genetically-encoded-bret-probes-shed-light-on-ligand-bias-induced-variable-ion-selectivity-in-trpv1-and-p2x5-7\/"},"modified":"2023-02-17T07:15:33","modified_gmt":"2023-02-17T07:15:33","slug":"2022-genetically-encoded-bret-probes-shed-light-on-ligand-bias-induced-variable-ion-selectivity-in-trpv1-and-p2x5-7","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2022-genetically-encoded-bret-probes-shed-light-on-ligand-bias-induced-variable-ion-selectivity-in-trpv1-and-p2x5-7\/","title":{"rendered":"2022- Genetically-encoded BRET probes shed light on ligand bias\u2013induced variable ion selectivity in TRPV1 and P2X5\/7"},"content":{"rendered":"<p>Whether ion channels experience ligand-dependent dynamic ion selectivity remains of critical importance since this could support ion channel functional bias. Tracking selective ion permeability through ion channels, however, remains challenging even with patch-clamp electrophysiology. In this study, we have developed highly sensitive bioluminescence resonance energy transfer (BRET) probes providing dynamic measurements of Ca<sup>2+<\/sup> and K<sup>+<\/sup> concentrations and ionic strength in the nanoenvironment of Transient Receptor Potential Vanilloid-1 Channel (TRPV1) and P2X channel pores in real time and in live cells during drug challenges. Our results indicate that AMG517, BCTC, and AMG21629, three well-known TRPV1 inhibitors, more potently inhibit the capsaicin (CAPS)-induced Ca<sup>2+<\/sup> influx than the CAPS-induced K<sup>+<\/sup> efflux through TRPV1. Even more strikingly, we found that AMG517, when injected alone, is a partial agonist of the K<sup>+<\/sup> efflux through TRPV1 and triggers TRPV1-dependent cell membrane hyperpolarization. In a further effort to exemplify ligand bias in other families of cationic channels, using the same BRET-based strategy, we also detected concentration- and time-dependent ligand biases in P2X7 and P2X5 cationic selectivity when activated by benzoyl-adenosine triphosphate (Bz-ATP). These custom-engineered BRET-based probes now open up avenues for adding value to ion-channel drug discovery platforms by taking ligand bias into account.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[55,56],"target_categories":[337,338],"target_families":[339],"targets":[101],"resource_keyword":[],"class_list":["post-6681","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","therapeutic_areas-cns","therapeutic_areas-pain","target_categories-ligand-gated-ion-channels","target_categories-other-ion-channels","target_families-trp-channels","targets-trpv1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6681","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=6681"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6681"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6681"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6681"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6681"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6681"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6681"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6681"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6681"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}