Effects of Proton Irradiation on Ionic Currents and Gene Expression in Human and Rodent Cell Lines

Most mammalian cells express a wide range of potassium (K+) channels, such as large conductance K+ (BK) and voltage gated K+ (Kv) channels. In non-excitable cells, K+ channels are involved in volume regulation, hormonal secretion, cell proliferation, migration and apoptosis [1,2]. The ability of ion channels to act as modulators of conductance is due to their innate property of rapid conformational alterations to initiate or respond to signal transduction [3]. Several lines of evidence from molecular, biochemical, and biological studies outline that different pathways are operating in cells and organisms at low and high radiation doses leading to a non linearity in the dose–response increase. A previous study performed in human cell lines showed that both normal and cancer cells exhibit an increase in Kv currents after treatment with low dose ionizing radiation (LDIR), suggesting that K+ current (IK) modifications are acting as a component of a signal transduction pathway(s) in response to stress, such as amplification of reactive oxygen species (ROS) signaling cascade [4]. Moreover, it has been shown that ionizing radiation (IR) might directly modify BK channel activity and therefore modulate cytosolic free Ca++ concentration and CAMKII pathway [5]. In this work, we studied the effects of proton (H+) irradiation at different doses (from 0.25 to 4 Gy) on wholecell IK and gene expression in a rodent and a human cell system: Chinese hamster lung fibroblasts (V79) and glioblastoma multiform cell line (T98G) respectively.