Titushkin, I. A., Rao, V. S., Pickard, W. F., Moros, E. G., Shafirstein, G. and Cho, M. R. Altered Calcium Dynamics Mediates P19-Derived Neuron-Like Cell Responses to Millimeter-Wave Radiation.
Intracellular calcium oscillations have long been recognized as a principal mediator of many vital cellular activities. Furthermore, Ca2 dynamics can be modulated by external physical cues, including electromagnetic fields. While cellular responses to low-frequency electric fields have been established, the possible non-thermal effects of millimeter-wave (MMW) radiation are still a subject of discussion and debate. We used mouse embryonic stem cell-derived neuronal cells and a custom-built 94 GHz applicator to examine in real time the altered Ca2 oscillations associated with MMW stimulation. MMW irradiation at 18.6 kW/m2 nominal power density significantly increased the Ca2 spiking frequency in the cells exhibiting Ca2 activity. The N-type calcium channels, phospholipase C enzyme, and actin cytoskeleton appear to be involved in mediating increased Ca2 spiking. Reorganization of the actin microfilaments by a 94 GHz field seems to play a crucial role in modulating not only Ca2 activity but also cell biomechanics. Many but not all observed cellular responses to MMW were similar to thermally induced effects. For example, cell exposure to a 94 GHz field induced nitric oxide production in some morphologically distinct neuronal cells that could not be reproduced by thermal heating of the cells up to 42°C. The highest observed average temperature rise in the MMW exposure chamber was ∼8°C above the room temperature, with possible complex non-uniform microscopic distribution of heating rates at the cell level. Our findings may be useful to establish quantitative molecular benchmarks for elucidation of nociception mechanisms and evaluation of potential adverse bioeffects associated with MMW exposure. Moreover, control of Ca2 dynamics by MMW stimulation may offer new tools for regulation of Ca2 -dependent cellular and molecular activities, for example, in tissue engineering applications.
