Effects of electromagnetic fields on neuronal ion channels: a systematic review

Annals of the New York Academy of Sciences · 2021 · Mixed · High evidence

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MixedHigh evidencePaper 1145

Study snapshot

PublicationAnnals of the New York Academy of Sciences · 2021

Study typesystematic_review

Reported directionMixed

Evidence ratingHigh

Abstract

Effects of electromagnetic fields on neuronal ion channels: a systematic review Federico Bertagna, Rebecca Lewis, S Ravi P Silva, Johnjoe McFadden, Kamalan Jeevaratnam. Effects of electromagnetic fields on neuronal ion channels: a systematic review. Ann N Y Acad Sci. 2021 May 4. doi: 10.1111/nyas.14597. Abstract Many aspects of chemistry and biology are mediated by electromagnetic field (EMF) interactions. The central nervous system (CNS) is particularly sensitive to EMF stimuli. Studies have explored the direct effect of different EMFs on the electrical properties of neurons in the last two decades, particularly focusing on the role of voltage- gated ion channels (VGCs). This work aims to systematically review published evidence in the last two decades detailing the effects of EMFs on neuronal ion channels as per the PRISM guidelines. Following a predetermined exclusion and inclusion criteria, 22 papers were included after searches on three online databases. Changes in calcium homeostasis, attributable to the voltage-gated calcium channels, were found to be the most commonly reported result of EMF exposure. EMF effects on the neuronal landscape appear to be diverse and greatly dependent on parameters, such as the field's frequency, exposure time, and intrinsic properties of the irradiated tissue, such as the expression of VGCs. Here, we systematically clarify how neuronal ion channels are particularly affected and differentially modulated by EMFs at multiple levels, such as gating dynamics, ion conductance, concentration in the membrane, and gene and protein expression. Ion channels represent a major transducer for EMF-related effects on the CNS. pubmed.ncbi.nlm.nih.gov Excerpts Different effects for different fields An extensive literature exists reporting a myriad of EMF exposure–related effects on many biological processes, ranging from cell differentiation, survival, and changes in gene expression96, 97 to effects on cell membranes and signal transduction pathways.30 However, many other studies indicated the absence of significant effects elicited by these fields.59, 61 A possible explanation for the different effects reported could be related to the fact that the way in which EMFs interact with the body depends on what combination of frequencies are used and the related wavelengths. It is well known that the effects of exposure to EMFs differ significantly based on the exposure intensities and the exposure time, 1, 98 and because of this any reasonable comparison must be made between groups having the same experimental conditions. In this study, we found different types of EMFs employed, although the two most commonly represented categories were ELF-EMFs and RF-EMFs, in line with the well-documented biological relevance of these fields. 94, 99, 100 It is important to point out that the effects exerted by these two types of exposures are not equal due to the intrinsic electrical properties of the neuronal membrane. For instance, electrical phenomena involving a redistribution of charges in the membrane subsequent to EMF exposure, such as counterion polarization and phospholipid reorientation, are not likely to occur in RF-EMF exposure, due to the high inertia of charged particles at this high frequency. 101 Moreover, pulsed EMFs are often reported to be more active relative to static EMFs, which are characterized by a continuous electromagnetic wave to which the cell could be more adapted,102 and they could affect the gating properties of VGCs since these proteins are intrinsically sensitive to minimal electrical variations. 100 Likewise, the effect of SMFs could similarly influence VGCs through a deformation of the membrane involving a reorientation of the phospholipid bilayer, as suggested by Rosen's study. 103 Indeed, both of the studies reviewed here that focused on SMF effects reported effects on VGCs, specifically on the gating dynamics of VGCCs47 and the inactivation dynamics of VGPCs. 46 Lastly, it is worth mentioning that the frequency-related impact of the various type of EMFs has not been totally clarified, and theories exist suggesting that only specific frequencies would relevantly interact with the cell. 104- 106 However, although many different types of fields have been used, the frequencies used were similar (specifically 50 Hz for ELF-EMFs and 835 and 900 Hz for RF-EMFs). Conclusion The studies reviewed here show VGCs as an important transducer of the effect of EMFs in neurons, and the central role played by these proteins in the regulation of important biological processes, central in the regulation of brain physiology, sheds a light on the influence that modern exposure to EMFs could have on human health. While a diverse range of biological systems were used, cell lines were the preferred option, and VGCCs were the most studied ion channels, in line with their central role in the regulation of many physiological processes in neurons. However, many other VGCs have been shown to be affected by EMFs and the results are often conflicting. In spite of the controversy, this systematic review reports significant correlation between EMFs and multiple changes in the electrophysiological properties of diverse neuronal tissues, and these results, if interpreted well, could pave the way to a new understanding of the relationship between electromagnetic stimulation and brain functions. In conclusion, we systematically demonstrate how the complex effects of EMFs in neuronal ion channels are exerted at multiple levels and how their significance in the alteration of neuronal functions is strictly dependent on different parameters relative to the type of field used and the studied cell or tissue. Improved experimental reproducibility will be key to any advances in this field, and the development of new experimental procedures capable of measuring the small but profound way in which certain types of EMF exposure seem to affect our brain might help us to establish whether it is harmful and its therapeutic potential. We hope this work will help in improving our knowledge about the molecular dynamics of neuronal VGCs, which will be key both for any progress in the treatment of neurodegenerative diseases and for an advancement in the general understanding of the relationship between technological progress and cellular dynamics.

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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 typesystematic_review

Effect directionmixed

PopulationNot supplied

Sample size22

ExposureNot supplied

Evidence strengthHighConfidence: 74% · Peer reviewed: yes

Main findings

This systematic review (22 included papers) reports that changes in calcium homeostasis attributable to voltage-gated calcium channels were the most commonly reported outcome of EMF exposure. The review describes diverse and parameter-dependent effects of EMFs on neuronal ion channels (e.g., gating dynamics, conductance, membrane concentration, and gene/protein expression), while also noting that results across studies are often conflicting and that some studies report no significant effects.

Outcomes measured

Neuronal ion channel modulation (voltage-gated ion channels)
Calcium homeostasis (voltage-gated calcium channels)
Electrophysiological properties of neuronal tissues
Ion channel gating dynamics
Ion conductance
Ion channel membrane concentration
Ion channel gene and protein expression

Limitations

Findings across included studies are reported as often conflicting.
Effects appear highly dependent on exposure parameters (e.g., frequency, exposure time) and tissue/cell properties, limiting comparability.
The review notes that many studies indicated absence of significant effects, suggesting heterogeneity in results.
Cell lines were the preferred model system among included studies (limited direct human inference).
The authors emphasize the need for improved experimental reproducibility.

View raw extracted JSON

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  "outcomes": [
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  "main_findings": "This systematic review (22 included papers) reports that changes in calcium homeostasis attributable to voltage-gated calcium channels were the most commonly reported outcome of EMF exposure. The review describes diverse and parameter-dependent effects of EMFs on neuronal ion channels (e.g., gating dynamics, conductance, membrane concentration, and gene/protein expression), while also noting that results across studies are often conflicting and that some studies report no significant effects.",
  "effect_direction": "mixed",
  "limitations": [
    "Findings across included studies are reported as often conflicting.",
    "Effects appear highly dependent on exposure parameters (e.g., frequency, exposure time) and tissue/cell properties, limiting comparability.",
    "The review notes that many studies indicated absence of significant effects, suggesting heterogeneity in results.",
    "Cell lines were the preferred model system among included studies (limited direct human inference).",
    "The authors emphasize the need for improved experimental reproducibility."
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  "summary": "This systematic review assessed published evidence from the last two decades on how electromagnetic fields affect neuronal voltage-gated ion channels, including 22 papers. It reports that altered calcium homeostasis linked to voltage-gated calcium channels was the most commonly described finding, and that EMF-related effects may occur at multiple levels (e.g., gating, conductance, and gene/protein expression). The review also emphasizes that results are heterogeneous and sometimes conflicting, with some studies reporting no significant effects, and that outcomes depend strongly on exposure and tissue parameters.",
  "key_points": [
    "The review followed PRISM guidelines and included 22 papers after database searches and eligibility screening.",
    "Changes in calcium homeostasis attributed to voltage-gated calcium channels were the most commonly reported EMF-related result.",
    "Reported EMF effects on neuronal ion channels were described as diverse and dependent on frequency, exposure time, and tissue/cell properties.",
    "The review summarizes modulation at multiple levels, including gating dynamics, ion conductance, membrane concentration, and gene/protein expression.",
    "ELF-EMFs and RF-EMFs were the most commonly represented exposure categories in the included literature.",
    "The authors note that some studies report no significant effects and that overall results are often conflicting.",
    "Improved experimental reproducibility is highlighted as important for clarifying potential harm versus therapeutic potential."
  ],
  "categories": [
    "Systematic Reviews",
    "Mechanisms",
    "Neuroscience"
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  "tags": [
    "Systematic Review",
    "Neuronal Ion Channels",
    "Voltage-Gated Ion Channels",
    "Voltage-Gated Calcium Channels",
    "Calcium Homeostasis",
    "Electrophysiology",
    "ELF-EMF",
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    "Gating Dynamics",
    "Gene Expression",
    "Protein Expression",
    "Central Nervous System"
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    "electromagnetic fields",
    "neurons",
    "central nervous system",
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    "ELF-EMF",
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    "gating dynamics",
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    "gene expression"
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  "social": {
    "tweet": "Systematic review (22 papers) on EMFs and neuronal ion channels reports commonly described changes in calcium homeostasis (VGCC-related) and parameter-dependent effects on gating, conductance, and expression—while noting heterogeneous and sometimes conflicting findings.",
    "facebook": "A systematic review of 22 studies on electromagnetic fields and neuronal ion channels reports that altered calcium homeostasis (linked to voltage-gated calcium channels) is the most commonly described outcome. The authors highlight diverse, parameter-dependent effects and note that findings across studies can be conflicting, underscoring the need for better reproducibility.",
    "linkedin": "This systematic review (22 included papers) examines how electromagnetic fields may modulate neuronal voltage-gated ion channels. It reports commonly described changes in calcium homeostasis (VGCC-related) and summarizes effects across multiple levels (gating, conductance, membrane concentration, gene/protein expression), while emphasizing heterogeneity and the need for improved experimental reproducibility."
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Identifiers and source

DOI: 10.1111/nyas.14597
PubMed: 33945157

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