Rao, V. S., Titushkin, I. A., Moros, E. G., Pickard, W. F., Thatte, H. S. and Cho, M. R. Nonthermal Effects of Radiofrequency-Field Exposure on Calcium Dynamics in Stem Cell-Derived Neuronal Cells: Elucidation of Calcium Pathways. Radiat. Res. 169, 319–329 (2008).

Intracellular Ca² spikes trigger cell proliferation, differentiation and cytoskeletal reorganization. In addition to Ca² spiking that can be initiated by a ligand binding to its receptor, exposure to electromagnetic stimuli has also been shown to alter Ca² dynamics. Using neuronal cells differentiated from a mouse embryonic stem cell line and a custom-built, frequency-tunable applicator, we examined in real time the altered Ca² dynamics and observed increases in the cytosolic Ca² in response to nonthermal radiofrequency (RF)-radiation exposure of cells from 700 to 1100 MHz. While about 60% of control cells (not exposed to RF radiation) were observed to exhibit about five spontaneous Ca² spikes per cell in 60 min, exposure of cells to an 800 MHz, 0.5 W/kg RF radiation, for example, significantly increased the number of Ca² spikes to 15.7 ± 0.8 (P < 0.05). The increase in the Ca² spiking activities was dependent on the frequency but not on the SAR between 0.5 to 5 W/kg. Using pharmacological agents, it was found that both the N-type Ca² channels and phospholipase C enzymes appear to be involved in mediating increased Ca² spiking. Interestingly, microfilament disruption also prevented the Ca² spikes. Regulation of Ca² dynamics by external physical stimulation such as RF radiation may provide a noninvasive and useful tool for modulating the Ca² -dependent cellular and molecular activities of cells seeded in a 3D environment for which only a few techniques are currently available to influence the cells.