TY - JOUR T1 - Oxidative Stress Activates Membrane Ion Channels in Human Biliary Epithelial Cancer Cells (Mz-Cha-1) JF - Anticancer Research JO - Anticancer Res SP - 5881 LP - 5888 VL - 35 IS - 11 AU - THORSTEN SCHLENKER AU - LUKAS SCHWAKE AU - AGNIESZKA VOSS AU - WOLFGANG STREMMEL AU - CHRISTOPH ELSING Y1 - 2015/11/01 UR - http://ar.iiarjournals.org/content/35/11/5881.abstract N2 - Oxidative stress is known to contribute to cell damage. In several cell types, one of the earliest effects of oxidative stress is a rapid and substantial decrease in cell volume, which in turn regulates a broad range of cell functions, including development of apoptosis. Since volume regulation is closely coupled to membrane ion permeability, activation of ion channels may play an important role in oxidative stress-related cell injury. Oxidative stress plays a major role in a variety of liver diseases and bile duct epithelia cells (BDE) represent an important site of injury. We, therefore, investigated the functional interactions of oxidative stress, cell volume and ion permeability in a BDE model. Whole-cell patch clamp studies were performed in the human Mz-Cha 1 cell line. Oxidative stress was produced by addition of H2O2 to the bath solution. Changes of intracellular Ca2+ concentration and of crosssectional area (for calculating cell volume) were monitored by laser scanning microscopy. Exposure of Mz-Cha 1 cells to H2O2 resulted in cell shrinkage and increase of the intracellular Ca2+ concentration. Patch-clamp studies revealed that exposure to H2O2 also resulted in the activation of ion currents with a threshold of 10−6 M H2O2. Ion substitution studies and blocker experiments identified the currents as representing an increase in membrane K+ and Cl-permeability. Interestingly both ion channel activation and cell shrinkage had a close relationship to the applied H2O2 concentration and were significantly inhibited by intracellular Ca2+ chelation. These data imply that in a BDE model, oxidative stress leads to cell shrinkage through activation of Ca2+-dependent K+ and Cl− currents. Since cell shrinkage has been associated with increased cell damage, the opening of these ion channels might contribute to the high susceptibility of biliary epithelial cancer cells to oxidative stress. ER -