{"id":17935,"date":"2025-08-29T09:24:09","date_gmt":"2025-08-29T07:24:09","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=17935"},"modified":"2026-03-27T10:18:26","modified_gmt":"2026-03-27T08:18:26","slug":"2025-fgf14-peptide-derivative-differentially-regulates-nav1-2-and-nav1-6-function","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2025-fgf14-peptide-derivative-differentially-regulates-nav1-2-and-nav1-6-function\/","title":{"rendered":"2025 &#8211; FGF14 Peptide Derivative Differentially Regulates Nav1.2 and Nav1.6 Function"},"content":{"rendered":"<p>Voltage-gated Na<sup>+<\/sup>\u00a0channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na<sup>+<\/sup>\u00a0channel isoforms (Nav1.1\u2013Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the \u03b1-subunit coded by each of the nine isoforms can sufficiently confer transient Na<sup>+<\/sup>\u00a0currents (I<sub>Na<\/sub>), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein\u2013protein interaction (PPI), and probes developed from iFGF\/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14\/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated I<sub>Na<\/sub><sup>+<\/sup>. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177\u2019s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress I<sub>Na<\/sub>\u00a0in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42,45,41],"resource_type":[75],"application_areas":[50,53,76],"therapeutic_areas":[55,143],"target_categories":[61],"target_families":[332],"targets":[],"resource_keyword":[],"class_list":["post-17935","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","products_tags-port-a-patch","products_tags-buffer-solutions","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","application_areas-drug-discovery","therapeutic_areas-cns","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels","target_families-nav-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/17935","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=17935"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=17935"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=17935"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=17935"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=17935"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=17935"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=17935"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=17935"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=17935"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}