Potassium channels as operators of alveolar epithelial repair

Abstract

A common feature of inflammatory lung diseases such as acute lung injury and acute respiratory distress syndrome (ARDS) is extensive damage and remodeling of alveolar epithelium. A better understanding of determinants of alveolar regeneration is thus necessary to develop strategies able to restore alveolar integrity. Recent studies have shown that K+ channels (KCh) are key components of cell proliferation and migration processes, necessary for tissues repair. We therefore postulated that KCh play a role in respiratory epithelial repair.Using a wound‐healing assay, we first showed that glibenclamide and clofilium, inhibitors of KATP and KvLQT1 channels, decrease repair rates of A549 and primary alveolar ATII cell monolayers and their inhibitory effects are additive. The role of KvLQT1 and KATP was then confirmed by a molecular approach using specific siRNAs. On the contrary, KvLQT1 and KATP activators significantly stimulate the wound repair. We also evaluated the influence of KCh on cell growth and we showed that clofilium dose‐dependently inhibits alveolar cell growth and induces an accumulation of cells arrested in G0/G1 phase.In conclusion, we demonstrated that KCh, particularly KvLQT1 and KATP, are involved in epithelial repair processes and should be identify as novel targets to promote alveolar repair necessary to ARDS resolution.Project funded by Canadian Institute of Health Research.