{"id":19595,"date":"2026-06-17T10:28:06","date_gmt":"2026-06-17T08:28:06","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=19595"},"modified":"2026-06-17T10:28:06","modified_gmt":"2026-06-17T08:28:06","slug":"2026-resolving-three-gaba-induced-electrogenic-events-and-gaba-coupling-stoichiometry-for-na-and-cl%e2%88%92-in-hgat-1","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2026-resolving-three-gaba-induced-electrogenic-events-and-gaba-coupling-stoichiometry-for-na-and-cl%e2%88%92-in-hgat-1\/","title":{"rendered":"2026 &#8211; Resolving three GABA induced electrogenic events and GABA-coupling stoichiometry for Na+ and Cl\u2212 in hGAT-1"},"content":{"rendered":"<p>GAT-1 is a neurotransmitter:sodium symporter responsible for the reuptake of GABA from the synaptic cleft. Because of its involvement in various pathological conditions, it is an important target for drug development; however, its mechanism of action remains under debate. Using high-resolution solid-supported membrane-based electrophysiology, we identified three sequential electrogenic events (E1, E2, and E3) in human GAT-1-mediated GABA transport. E1 reflects the transition to an occluded intermediate, upon GABA binding to the Na<sup>+<\/sup>\u00a0bound carrier; E2 was attributed to an uncoupled Na<sup>+<\/sup>\u00a0conductance triggered by GABA binding, while E3 represents Na<sup>+<\/sup>-coupled GABA transport. This triphasic model provides a robust electrophysiological framework for dissecting individual molecular transitions in the GAT-1 transport cycle. We also established a 2\u2009:\u20091 stoichiometry for Na<sup>+<\/sup>\u2009:\u2009GABA cotransport under standard conditions. However, this stoichiometric relationship breaks down under conditions of steep transmembrane Na<sup>+<\/sup>\u00a0gradients, which promote an uncoupled Na<sup>+<\/sup>\u00a0leak current. Our data further suggests that Cl<sup>\u2212<\/sup>\u00a0translocation is not coupled to GABA transport. These findings refine the current understanding of the GAT-1 transport mechanism, providing a foundation to support the development of novel therapeutics.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[36],"resource_type":[75],"application_areas":[53,108],"therapeutic_areas":[55,143],"target_categories":[60],"target_families":[503],"targets":[331],"resource_keyword":[],"class_list":["post-19595","resource_library","type-resource_library","status-publish","hentry","products_tags-surfe2r-n1","resource_type-publication","application_areas-assay-development-and-validation","application_areas-transporters","therapeutic_areas-cns","therapeutic_areas-assay-development-and-validation","target_categories-transporters","target_families-solute-carrier-family-slc","targets-gat1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/19595","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=19595"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=19595"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=19595"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=19595"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=19595"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=19595"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=19595"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=19595"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=19595"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}