Many tumor cells express highly elevated activities of voltage-gated potassium channels in the plasma membrane which are indispensable for tumor development. To test for potassium channel function in response to genotoxic stress, human erythroleukemia K562 cells were subjected to sub-lethal doses of ionizing radiation (IR, 1 or 5 Gy). Potassium channel activity was determined by whole-cell patch clamp recording and cell cycle progression by flow cytometry. As a result, IR stimulated an increase in the activity of Herg-like and other voltage-gated potassium channels which became apparent 1.5 h post-IR. In addition, the higher dose (5 Gy) altered the voltage dependence of the Herg-like currents suggestive of an increase in the fractional activity of the Herg1b isoform. The IR-stimulated modulation of the potassium conductance was followed by a G2/M cell cycle arrest as analyzed 8 h to 48 h post-IR. Depolarizing the membrane potential by high extracellular potassium concentrations (50 mM) or inhibiting Herg1 channels with E4031 (30 mM) delayed the G1/S transition and the accumulation in G2 phase of cell cycle in irradiated cells but had no effect on cell cycle progression of non-irradiated control cells. Taken together, this suggests a specific function of Herg1 potassium channels for the cell cycle control of K562 cells after genotoxic stress.