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 achieved 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 regulatory volume decrease (RVD) in ciliated epithelial cells from murine trachea. RVD was inhibited by tamoxifen and 1,9-dideoxyforskolin, two agents that 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. Ba(2+) and apamin, inhibitors of K(+) channels, were without effect on RVD, while tetraethylammoniun had little effect on RVD. In contrast, clofilium, an inhibitor of the KvLQT/IsK potassium channel complex potently inhibited RVD, suggesting a role for the KvLQT/IsK channel complex in cell volume regulation by tracheal epithelial cells. To investigate further the role of KvLQT/IsK channels in RVD, we used IsK knock-out mice. When exposed to hypotonic solutions, tracheal cells from IsK(+/+) mice underwent RVD, whereas cells from IsK(-/-) failed to recover their normal size. These data suggest that the IsK potassium subunit plays an important role in RVD in murine tracheal epithelial cells.