Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects

J Cell Mol Med · 2013 · Mixed · Low evidence

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MixedLow evidencePaper 2424

Study snapshot

PublicationJ Cell Mol Med · 2013

Study typereview

Reported directionMixed

Evidence ratingLow

Abstract

The direct targets of extremely low and microwave frequency range electromagnetic fields (EMFs) in producing non-thermal effects have not been clearly established. However, studies in the literature, reviewed here, provide substantial support for such direct targets. Twenty-three studies have shown that voltage-gated calcium channels (VGCCs) produce these and other EMF effects, such that the L-type or other VGCC blockers block or greatly lower diverse EMF effects. Furthermore, the voltage-gated properties of these channels may provide biophysically plausible mechanisms for EMF biological effects. Downstream responses of such EMF exposures may be mediated through Ca2+/calmodulin stimulation of nitric oxide synthesis. Potentially, physiological/therapeutic responses may be largely as a result of nitric oxide-cGMP-protein kinase G pathway stimulation. A well-studied example of such an apparent therapeutic response, EMF stimulation of bone growth, appears to work along this pathway. However, pathophysiological responses to EMFs may be as a result of nitric oxide-peroxynitrite-oxidative stress pathway of action. A single such well-documented example, EMF induction of DNA single-strand breaks in cells, as measured by alkaline comet assays, is reviewed here. Such single-strand breaks are known to be produced through the action of this pathway. Data on the mechanism of EMF induction of such breaks are limited; what data are available support this proposed mechanism. Other Ca2+-mediated regulatory changes, independent of nitric oxide, may also have roles. This article reviews, then, a substantially supported set of targets, VGCCs, whose stimulation produces non-thermal EMF responses by humans/higher animals with downstream effects involving Ca2+/calmodulin-dependent nitric oxide increases, which may explain therapeutic and pathophysiological effects.

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typereview

Effect directionmixed

Populationhumans/higher animals (as described in review)

Sample sizeNot supplied

ExposureELF and microwave

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

This review summarizes literature suggesting that non-thermal EMF effects (ELF and microwave range) can be reduced or blocked by L-type or other VGCC blockers, supporting VGCCs as direct targets. It proposes downstream signaling via Ca2+/calmodulin-dependent nitric oxide pathways that may underlie both therapeutic effects (e.g., bone growth stimulation) and adverse effects (e.g., DNA single-strand breaks via oxidative stress/peroxynitrite).

Outcomes measured

Voltage-gated calcium channel (VGCC) activation/blockade effects
Nitric oxide signaling changes (Ca2+/calmodulin-dependent)
Bone growth stimulation (therapeutic response example)
DNA single-strand breaks (alkaline comet assay example)
Oxidative stress/peroxynitrite pathway involvement

Limitations

Narrative review; no systematic methods described in abstract
Mechanistic data for EMF induction of DNA single-strand breaks described as limited
Specific exposure parameters (frequency, intensity/SAR, duration) not provided in abstract
Examples of therapeutic and adverse effects are limited in number as described (bone growth; single-strand breaks)

View raw extracted JSON

{
  "study_type": "review",
  "exposure": {
    "band": "ELF and microwave",
    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": "humans/higher animals (as described in review)",
  "sample_size": null,
  "outcomes": [
    "Voltage-gated calcium channel (VGCC) activation/blockade effects",
    "Nitric oxide signaling changes (Ca2+/calmodulin-dependent)",
    "Bone growth stimulation (therapeutic response example)",
    "DNA single-strand breaks (alkaline comet assay example)",
    "Oxidative stress/peroxynitrite pathway involvement"
  ],
  "main_findings": "This review summarizes literature suggesting that non-thermal EMF effects (ELF and microwave range) can be reduced or blocked by L-type or other VGCC blockers, supporting VGCCs as direct targets. It proposes downstream signaling via Ca2+/calmodulin-dependent nitric oxide pathways that may underlie both therapeutic effects (e.g., bone growth stimulation) and adverse effects (e.g., DNA single-strand breaks via oxidative stress/peroxynitrite).",
  "effect_direction": "mixed",
  "limitations": [
    "Narrative review; no systematic methods described in abstract",
    "Mechanistic data for EMF induction of DNA single-strand breaks described as limited",
    "Specific exposure parameters (frequency, intensity/SAR, duration) not provided in abstract",
    "Examples of therapeutic and adverse effects are limited in number as described (bone growth; single-strand breaks)"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "electromagnetic fields",
    "ELF",
    "microwave",
    "non-thermal effects",
    "voltage-gated calcium channels",
    "VGCC blockers",
    "L-type calcium channels",
    "calcium signaling",
    "calmodulin",
    "nitric oxide",
    "cGMP",
    "protein kinase G",
    "peroxynitrite",
    "oxidative stress",
    "bone growth",
    "DNA single-strand breaks",
    "alkaline comet assay"
  ],
  "suggested_hubs": [
    {
      "slug": "who-icnirp",
      "weight": 0.2,
      "reason": "Mechanistic review relevant to non-thermal EMF effects that may intersect with exposure guideline discussions."
    }
  ]
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1111/jcmm.12088
PubMed: 23802593

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