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.

AI evidence extraction

Main findings

Real-time measurements showed increased cytosolic Ca(2+) and increased Ca(2+) spiking in response to nonthermal RF exposure from 700–1100 MHz. Example given: 800 MHz at 0.5 W/kg increased spikes to 15.7±0.8 vs ~5 spikes/cell/60 min in controls (P<0.05). The increase depended on frequency but not on SAR between 0.5–5 W/kg; pharmacological agents implicated N-type Ca(2+) channels and phospholipase C, and microfilament disruption prevented Ca(2+) spikes.

Outcomes measured

• Cytosolic Ca(2+) levels
• Number of intracellular Ca(2+) spikes
• Involvement of N-type Ca(2+) channels
• Involvement of phospholipase C enzymes
• Effect of microfilament disruption on Ca(2+) spiking

Limitations

• Sample size not reported in abstract
• Exposure source and detailed dosimetry beyond frequency range and SAR range not fully described in abstract
• Findings are from an in vitro mouse stem cell-derived neuronal model; generalizability to in vivo/humans not addressed in abstract

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "RF",
        "source": null,
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": "60 min"
    },
    "population": "Neuronal cells differentiated from a mouse embryonic stem cell line (in vitro)",
    "sample_size": null,
    "outcomes": [
        "Cytosolic Ca(2+) levels",
        "Number of intracellular Ca(2+) spikes",
        "Involvement of N-type Ca(2+) channels",
        "Involvement of phospholipase C enzymes",
        "Effect of microfilament disruption on Ca(2+) spiking"
    ],
    "main_findings": "Real-time measurements showed increased cytosolic Ca(2+) and increased Ca(2+) spiking in response to nonthermal RF exposure from 700–1100 MHz. Example given: 800 MHz at 0.5 W/kg increased spikes to 15.7±0.8 vs ~5 spikes/cell/60 min in controls (P<0.05). The increase depended on frequency but not on SAR between 0.5–5 W/kg; pharmacological agents implicated N-type Ca(2+) channels and phospholipase C, and microfilament disruption prevented Ca(2+) spikes.",
    "effect_direction": "harm",
    "limitations": [
        "Sample size not reported in abstract",
        "Exposure source and detailed dosimetry beyond frequency range and SAR range not fully described in abstract",
        "Findings are from an in vitro mouse stem cell-derived neuronal model; generalizability to in vivo/humans not addressed in abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "radiofrequency",
        "RF",
        "nonthermal",
        "calcium dynamics",
        "Ca2+ spikes",
        "stem cell-derived neuronal cells",
        "mouse embryonic stem cell",
        "700–1100 MHz",
        "800 MHz",
        "SAR",
        "N-type calcium channels",
        "phospholipase C",
        "microfilaments",
        "cytoskeleton"
    ],
    "suggested_hubs": []
}

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