TASK-1 Channel Promotes Hydrogen Peroxide Induced Apoptosis

ABSTRACT

Hydrogen peroxide (H2O2) causes oxidative stress and is considered as an inducer of cell death in various tissues. Two-pore domain K+ (K2p) channels may mediate K+ efflux during apoptotic volume decreases (AVD) in zygotes and in mouse embryos. In the present study, we sought to elucidate linkage between K2p channels and cell death by H2O2. Thus K2p 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 H2O2 concentration. Ionic currents were recorded in cell-attached mode. The bath solution was the normal Ringer solution and the pipette solution was high K+ solution. In HEK-293 cells expressing TREK-1, TREK-2, TASK-3, H2O2 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 H2O2 induced cell death was increased. In cell attached-mode recording, application of H2O2 (300micrometer) increased activity of all K2P channels. However, a low concentration of H2O2 (50micrometer) increased only TASK-1 channel activity. These results indicate that TASK-1 might participate in K+ efflux by H2O2 at low concentration, thereby inducing AVD.