AbstractsBiology & Animal Science

Increasing evidence suggests that the activity of ion channels is intimately related to the control of the cell cycle and involved in a modulation of fundamental processes like apoptosis or proliferation and migration of cells. Because of this prominent role in the physiology of humans it is important to understand the impact of sparsely and densely ionizing irradiation on channel function in the context of exposure to natural radiation, radiotherapy and even space missions. The present experiments address the question on whether ionizing irradiation could have any implications on channel activity in the plasma membrane of mammalian cells. In particular there was a special focus on any fast events early on after treatment. For this purpose we examined the conductance of K + channels in mammalian cells by patch clamp technique before and soon after exposure to sparsely or densely ionizing irradiation. The possibility of electrophysiological recordings with a high temporal resolution makes it possible to observe the initial steps in signal transduction cascades. Our data show that radiation exposure to sparsely and densely ionizing irradiation results in an immediate activation of K channels in A549 cells and in human peripheral blood lymphocytes. The data stress that in particular the human intermediate Ca 2+ activated channel hIK + . With the use of specific blockers + channels. Experiments in which cells were challenged with H 2 O 2 or in which the cytosolic Ca 2+ buffer concentration was altered show that an increase in K + channel activity is presumably the result of a serial scenario: radiation causes an increase in radicals in the cytosol, which in turn triggers an elevation of [Ca 2+ ] ; the latter is the established trigger for hIK activation. Flow cytometry experiments in the presence and absence of hIK channel blockers show that these events are instrumental for the induction of proliferation and migration of hIK expressing cells. Altogether these data provide important insights into potential side effects of ionizing irradiation and they may be helpful to improve radiation therapy of cancer.