TASK-1 Channel Promotes Hydrogen Peroxide Induced Apoptosis

TASK-1 Channel Promotes Hydrogen Peroxide Induced Apoptosis

Hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>) causes oxidative stress and is considered as an inducer of cell death in various tissues. Two-pore domain K<SUP>&#8290;</SUP> (K<SUB>2p</SUB>) channels may mediate K<SUP>&#8290;</SUP> efflux during apoptotic volume decreases (AVD) in zygotes and in mouse embryos. In the present study, we sought to elucidate linkage between K<SUB>2p</SUB> channels and cell death by H<SUB>2</SUB>O<SUB>2</SUB>. Thus K<SUB>2p</SUB> channels (TASK-1, TASK-3, TREK-1, TREK-2) were stably transfected in HEK-293 cells, and cytotoxicity assay was preformed using cell counting kit-8 (CCK-8). Cell survival rates were calculated using the cytotoxicity assay data and dose-response curve was fitted to the H<SUB>2</SUB>O<SUB>2</SUB> concentration. Ionic currents were recorded in cell-attached mode. The bath solution was the normal Ringer solution and the pipette solution was high K<SUP>&#8290;</SUP> solution. In HEK-293 cells expressing TREK-1, TREK-2, TASK-3, H<SUB>2</SUB>O<SUB>2</SUB> induced cell death did not change in comparison to non-transfected HEK-293. In HEK-293 cells expressing TASK-1, however, dose-response curve was significantly shifted to the left. It means that H<SUB>2</SUB>O<SUB>2</SUB> induced cell death was increased. In cell attached-mode recording, application of H<SUB>2</SUB>O<SUB>2</SUB> (300μM) increased activity of all K<SUB>2P</SUB> channels. However, a low concentration of H<SUB>2</SUB>O<SUB>2</SUB> (50μM) increased only TASK-1 channel activity. These results indicate that TASK-1 might participate in K<SUP>&#8290;</SUP> efflux by H<SUB>2</SUB>O<SUB>2</SUB> at low concentration, thereby inducing AVD.