title: Nonthermal effects of radiofrequency-field exposure on calcium dynamics in stem cell-derived neuronal cells: elucidation of calcium pathways.
abstract: Intracellular Ca(2+) spikes trigger cell proliferation, differentiation and cytoskeletal reorganization. In addition to Ca(2+) spiking that can be initiated by a ligand binding to its receptor, exposure to electromagnetic stimuli has also been shown to alter Ca(2+) 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 Ca(2+) dynamics and observed increases in the cytosolic Ca(2+) 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 Ca(2+) 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 Ca(2+) spikes to 15.7+/-0.8 (P<0.05). The increase in the Ca(2+) 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 Ca(2+) channels and phospholipase C enzymes appear to be involved in mediating increased Ca(2+) spiking. Interestingly, microfilament disruption also prevented the Ca(2+) spikes. Regulation of Ca(2+) dynamics by external physical stimulation such as RF radiation may provide a noninvasive and useful tool for modulating the Ca(2+)-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.
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: V S
authors.initials: VS
authors.lastname: Rao
authors.forename: I A
authors.initials: IA
authors.lastname: Titushkin
authors.forename: E G
authors.initials: EG
authors.lastname: Moros
authors.forename: W F
authors.initials: WF
authors.lastname: Pickard
authors.forename: H S
authors.initials: HS
authors.lastname: Thatte
authors.forename: M R
authors.initials: MR
authors.lastname: Cho
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology / Q000528:radiation effects; D020013:Calcium Signaling / Q000502:physiology* / Q000528:radiation effects*; D002454:Cell Differentiation / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D006358:Hot Temperature; D008657:Metabolic Clearance Rate / Q000528:radiation effects; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects; D011829:Radiation Dosage; D011846:Radio Waves; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium