{"id":18718,"date":"2025-12-29T12:21:54","date_gmt":"2025-12-29T10:21:54","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=18718"},"modified":"2025-12-29T12:57:15","modified_gmt":"2025-12-29T10:57:15","slug":"2025-physiological-oxygen-levels-reset-k-channel-activity-in-human-vascular-endothelial-cells","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2025-physiological-oxygen-levels-reset-k-channel-activity-in-human-vascular-endothelial-cells\/","title":{"rendered":"2025 &#8211; Physiological oxygen levels reset K+ channel activity in human vascular endothelial cells"},"content":{"rendered":"<p>Human endothelial cells (EC) play a critical role in vascular homeostasis and their function is influenced by oxygen tension. This study investigates for the first time the effects of long-term adaptation (5 days) of two major EC types to physiological oxygen tension (5kPa) on basal and nitric oxide (NO)-modulated K<sup>+<\/sup>\u00a0channel activities. Whole-cell patch clamp experiments demonstrate that human umbilical vein EC (HUVEC) exhibit larger basal K<sup>+<\/sup>\u00a0outward and smaller inward currents under 5kPa O<sub>2<\/sub>\u00a0compared to standard hyperoxic (18kPa) culture conditions. Outward currents were potentiated by NO only under hyperoxia. Human cerebral microvascular EC (hCMEC\/D3) showed larger outward currents under 5kPa O<sub>2<\/sub>\u00a0which were further potentiated by NO. Pharmacological isolation of different K<sup>+<\/sup>\u00a0currents using tetraethylammonium, TRAM-34 and apamin revealed differential effects in EC adapted to 5kPa or 18kPa O<sub>2<\/sub>. Under 5kPa O<sub>2<\/sub>, both cell types show greater contributions of TEA-sensitive currents and in addition hCMEC\/D3 cells exhibit higher proportions of TRAM-34 and apamin-sensitive currents under 5kPa O<sub>2<\/sub>. In HUVEC, changes in half-activation voltage and hyperpolarized membrane potentials were detected only under hyperoxic conditions following NO exposure, with both cell types exhibiting altered current activation kinetics of outward and inward currents. Notably, expression of KCa3.1, KCa1.1, KCa2.3 and Kir6.1 channels was unaffected by O<sub>2<\/sub>, suggesting that changes in whole-cell currents in both EC types were due to channel modulation. Thus, our findings reveal that physiological O<sub>2<\/sub>\u00a0tension shapes the electrophysiological phenotype of human EC by modulating K<sup>+<\/sup>\u00a0channel function and NO responsiveness. The novel insights into the modulation of EC K<sup>+<\/sup>\u00a0channels by O<sub>2<\/sub>\u00a0has implications for the regulation of vascular tone and design and use of experimental models\u00a0<em>in vitro<\/em>\u00a0for high throughput drug discovery and clinical translation.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[50,53],"therapeutic_areas":[143],"target_categories":[338],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-18718","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","therapeutic_areas-assay-development-and-validation","target_categories-other-ion-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/18718","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=18718"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=18718"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=18718"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=18718"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=18718"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=18718"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=18718"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=18718"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=18718"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}