Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Deficiency of the two-pore-domain potassium channel TREK-1 promotes hyperoxia-induced lung injury.

Authors: Schwingshackl, Andreas; Teng, Bin; Makena, Patrudu; Ghosh, Manik; Sinclair, Scott E; Luellen, Charlean; Balasz, Louisa; Rovnaghi, Cynthia; Bryan, Robert M; Lloyd, Eric E; Fitzpatrick, Elizabeth; Saravia, Jordy S; Cormier, Stephania A; Waters, Christopher M

Published In Crit Care Med, (2014 Nov)

Abstract: We previously reported the expression of the two-pore-domain K channel TREK-1 in lung epithelial cells and proposed a role for this channel in the regulation of alveolar epithelial cytokine secretion. In this study, we focused on investigating the role of TREK-1 in vivo in the development of hyperoxia-induced lung injury.Laboratory animal experiments.University research laboratory.Wild-type and TREK-1-deficient mice.Mice were anesthetized and exposed to 1) room air, no mechanical ventilation, 2) 95% hyperoxia for 24 hours, and 3) 95% hyperoxia for 24 hours followed by mechanical ventilation for 4 hours.Hyperoxia exposure accentuated lung injury in TREK-1-deficient mice but not controls, resulting in increase in lung injury scores, bronchoalveolar lavage fluid cell numbers, and cellular apoptosis and a decrease in quasi-static lung compliance. Exposure to a combination of hyperoxia and injurious mechanical ventilation resulted in further morphological lung damage and increased lung injury scores and bronchoalveolar lavage fluid cell numbers in control but not TREK-1-deficient mice. At baseline and after hyperoxia exposure, bronchoalveolar lavage cytokine levels were unchanged in TREK-1-deficient mice compared with controls. Exposure to hyperoxia and mechanical ventilation resulted in an increase in bronchoalveolar lavage interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-α levels in both mouse types, but the increase in interleukin-6 and monocyte chemotactic protein-1 levels was less prominent in TREK-1-deficient mice than in controls. Lung tissue macrophage inflammatory protein-2, keratinocyte-derived cytokine, and interleukin-1β gene expression was not altered by hyperoxia in TREK-1-deficient mice compared with controls. Furthermore, we show for the first time TREK-1 expression on alveolar macrophages and unimpaired tumor necrosis factor-α secretion from TREK-1-deficient macrophages.TREK-1 deficiency resulted in increased sensitivity of lungs to hyperoxia, but this effect is less prominent if overwhelming injury is induced by the combination of hyperoxia and injurious mechanical ventilation. TREK-1 may constitute a new potential target for the development of novel treatment strategies against hyperoxia-induced lung injury.

PubMed ID: 25126877 Exiting the NIEHS site

MeSH Terms: Acute Lung Injury/etiology; Acute Lung Injury/pathology*; Acute Lung Injury/therapy; Animals; Blotting, Western; Bronchoalveolar Lavage Fluid/chemistry; Cytokines/genetics; Cytokines/metabolism*; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Hyperoxia/complications*; Macrophages, Alveolar/metabolism; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal/methods; Potassium Channels, Tandem Pore Domain/deficiency*; Potassium Channels, Tandem Pore Domain/metabolism; Random Allocation; Real-Time Polymerase Chain Reaction; Reference Values; Respiration, Artificial; Risk Assessment; Severity of Illness Index

Back
to Top