K_2P2.1 (TREK-1) potassium channel activation protects against hyperoxia-induced lung injury.

ABSTRACT: No targeted therapies exist to counteract Hyperoxia (HO)-induced Acute Lung Injury (HALI). We previously found that HO downregulates alveolar K_2P2.1 (TREK-1) K⁺ channels, which results in worsening lung injury. This decrease in TREK-1 levels leaves a subset of channels amendable to pharmacological intervention. Therefore, we hypothesized that TREK-1 activation protects against HALI. We treated HO-exposed mice and primary alveolar epithelial cells (AECs) with the novel TREK-1 activators ML335 and BL1249, and quantified physiological, histological, and biochemical lung injury markers. We determined the effects of these drugs on epithelial TREK-1 currents, plasma membrane potential (Em), and intracellular Ca²⁺ (iCa) concentrations using fluorometric assays, an

SUBMITTER: Zyrianova T 

PROVIDER: S-EPMC7738539 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature