Contribution of the IsK (MinK) potassium channel subunit to regulatory volume decrease in murine tracheal epithelial cells

The cell volume regulatory response following hypotonic shocks is often ach ieved by the coordinated activation of K+ and Cl- channels. In this study, we investigate the identity of the K+ and Cl- channels that mediate the reg ulatory volume decrease (RVD) in ciliated epithelial cells from murine trac hea. RVD was inhibited by tamoxifen and 1,9-dideoxyforskolin, two agents th at block swelling-activated Cl- channels. These data suggest that swelling- activated Cl- channels play an important role in cell volume regulation in murine tracheal epithelial cells. Ba2+ and apamin, inhibitors of K+ channel s, were without effect on RVD, while tetraethylammoniun had little effect o n RVD. In contrast, clofilium, an inhibitor of the KvLQT/IsK potassium chan nel complex potently inhibited RVD, suggesting a role for the KvLQT/IsK cha nnel complex in cell volume regulation by tracheal epithelial cells. To inv estigate further the role of KvLQT/IsK channels in RVD, we used IsK knock-o ut mice. When exposed to hypotonic solutions, tracheal cells from IsK(+/+) mice underwent RVD, whereas cells from IsK(-/-) failed to recover their nor mal size. These data suggest that the IsK potassium subunit plays an import ant role in RVD in murine tracheal epithelial cells.