K(Ca)3.1 K(+) Channel Expression and Function in Human Bronchial Epithelial Cells

The K(Ca)3.1 K(+) channel has been proposed as a novel target for pulmonary diseases such as asthma and pulmonary fibrosis. It is expressed in epithelia but its expression and function in primary human bronchial epithelial cells (HBECs) has not been described. Due to its proposed roles in the regulation of cell proliferation, migration, and epithelial fluid secretion, inhibiting this channel might have either beneficial or adverse effects on HBEC function. The aim of this study was to assess whether primary HBECs express the K(Ca)3.1 channel and its role in HBEC function. Primary HBECs from the airways of healthy and asthmatic subjects, SV-transformed BEAS-2B cells and the neoplastic H292 epithelial cell line were studied. Primary HBECs, BEAS-2B and H292 cells expressed K(Ca)3.1 mRNA and protein, and robust K(Ca)3.1 ion currents. K(Ca)3.1 protein expression was increased in asthmatic compared to healthy airway epithelium in situ, and K(Ca)3.1 currents were larger in asthmatic compared to healthy HBECs cultured in vitro. Selective K(Ca)3.1 blockers (TRAM-34, ICA-17043) had no effect on epithelial cell proliferation, wound closure, ciliary beat frequency, or mucus secretion. However, several features of TGFβ1-dependent epithelial-mesenchymal transition (EMT) were inhibited by K(Ca)3.1 blockade. Treatment with K(Ca)3.1 blockers is likely to be safe with respect to airway epithelial biology, and may potentially inhibit airway remodelling through the inhibition of EMT.