Nonthermal effects of radiofrequency-field exposure on calcium dynamics in stem cell-derived neuronal cells: Elucidation of calcium pathways

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. (C) 2008 by Radiation Research Society.