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


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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 Ca(2+) /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 Ca(2+) -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 Ca(2+) /calmodulin-dependent nitric oxide increases, which may explain therapeutic and pathophysiological effects.
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Electromagnetic fields act via activation of voltage-gated
calcium channels to produce beneficial or adverse effects
Martin L. Pall *
Professor Emeritus of Biochemistry and Basic Medical Sciences, Washington State University, Portland, OR, USA
Received: January 8, 2013; Accepted: May 20, 2013
Possible modes of action following
voltage-gated calcium channel stimulation
Therapeutic bone-growth stimulation
via Ca
/nitric oxide/cGMP/protein kinase G
/nitric oxide/peroxynitrite and
responses to EMF exposures: the example of
single-strand DNA breaks
Discussion and conclusions
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 Ca
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 path-
way 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 Ca
-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 Ca
/calmodulin-dependent nitric oxide
increases, which may explain therapeutic and pathophysiological effects.
Keywords: intracellular Ca
voltage-gated calcium channels
low frequency electromagnetic field exposure
oxidative stress
calcium channel blockers
An understanding of the complex biology of the effects of electromag-
netic fields (EMFs) on human/higher animal biology inevitably must
be derived from an understanding of the target or targets of such
fields in the impacted cells and tissues. Despite this, no understand-
ing has been forthcoming on what those targets are and how they
may lead to the complex biological responses to EMFs composed of
low-energy photons. The great puzzle, here, is that these EMFs are
comprised of low-energy photons, those with insufficient energy to
individually influence the chemistry of the cell, raising the question of
how non-thermal effects of such EMFs can possibly occur. The author
*Correspondence to: Martin L. PALL, Ph.D.,
Professor Emeritus of Biochemistry and Basic Medical
Sciences, Washington State University, 638 NE 41st Ave.,
Portland, OR 97232 USA
Tel: +01-503-232-3883
ª2013 The Author.
Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
doi: 10.1111/jcmm.12088
J. Cell. Mol. Med. Vol 17, No 8, 2013 pp. 958-965
has found that there is a substantial literature possibly pointing to the
direct targets of such EMFs and it is the goal of this study to review
that evidence as well as review how those targets may lead to the
complex biology of EMF exposure.
The role of increased intracellular Ca
following EMF exposure
was already well documented more than 20 years ago, when Wallec-
zek [1] reviewed the role of changes in calcium signalling that were
produced in response EMF exposures. Other, more recent studies
have confirmed the role of increased intracellular Ca
following EMF
exposure, a few of which are discussed below. His review [1]
included two studies [2, 3] that showed that the L-type voltage-gated
channel blocker, verapamil could lower or block changes in response
to EMFs. The properties of voltage-gated calcium channels (VGCCs)
have been reviewed elsewhere [4]. Subsequently, extensive evidence
has been published clearly showing that the EMF exposure can act to
produce excessive activity of the VGCCs in many cell types [526]
suggesting that these may be direct targets of EMF exposure. Many
of these studies implicate specifically the L-type VGCCs such that var-
ious L-type calcium channel blockers can block responses to EMF
exposure (Table 1). However, other studies have shown lowered
responses produced by other types of calcium channel blockers
including N-type, P/Q-type, and T-type blockers (Table 1), showing
that other VGCCs may have important roles. Diverse responses to
EMFs are reported to be blocked by such calcium channel blockers
(Table 1), suggesting that most if not all EMF-mediated responses
may be produced through VGCC stimulation. Voltage-gated calcium
channels are essential to the responses produced by extremely low
frequency (including 50/60 Hz) EMFs and also to microwave fre-
quency range EMFs, nanosecond EMF pulses, and static electrical
and magnetic fields (Table 1).
In a recent study, Pilla [27] showed that an increase in intracellu-
lar Ca
must have occurred almost immediately after EMF exposure,
producing a Ca
/calmodulin-dependent increase in nitric oxide
occurring in less than 5 sec. Although Pilla [27] did not test whether
VGCC stimulation was involved in his study, there are few alternatives
that can produce such a rapid Ca
response, none of which has been
implicated in EMF responses. Other studies, each involving VGCCs,
summarized in Table 1, also showed rapid Ca
increases following
EMF exposure [8, 16, 17, 19, 21]. The rapidity of these responses rule
out many types of regulatory interactions as being involved in produc-
ing the increased VGCC activity following EMF exposure and sug-
gests, therefore, that VGCC stimulation in the plasma membrane is
directly produced by EMF exposure.
Possible modes of action following
VGCC stimulation
The increased intracellular Ca
produced by such VGCC activation
may lead to multiple regulatory responses, including the increased
nitric oxide levels produced through the action of the two Ca
modulin-dependent nitric oxide synthases, nNOS and eNOS.
Increased nitric oxide levels typically act in a physiological context
through increased synthesis of cGMP and subsequent activation of
protein kinase G [28, 29]. In contrast, in most pathophysiological
contexts, nitric oxide reacts with superoxide to form peroxynitrite, a
potent non-radical oxidant [30, 31], which can produce radical prod-
ucts, including hydroxyl radical and NO
radical [32].
Therapeutic bone-growth stimulation
via Ca
/nitric oxide/cGMP/protein
kinase G
An example of a therapeutic effect for bone repair of EMF exposure in
various medical situations includes increasing osteoblast differentia-
tion and maturation and has been reviewed repeatedly [3344]. The
effects of EMF exposure on bone cannot be challenged, although
there is still considerable question about the best ways to apply this
clinically [3344]. Our focus, here, is to consider possible mecha-
nisms of action. Multiple studies have implicated increased Ca
nitric oxide in the EMF stimulation of bone growth [4449]; three
have also implicated increased cGMP and protein kinase G activity
[46, 48, 49]. In addition, studies on other regulatory stimuli leading to
increased bone growth have also implicated increased cGMP levels
and protein kinase G in this response [5056]. In summary, then, it
can be seen from the above that there is a very well-documented
action of EMFs in stimulating osteoblasts and bone growth. The avail-
able data, although limited, support the action of the main pathway
involved in physiological responses to Ca
and nitric oxide, namely
/nitric oxide/cGMP/protein kinase G in producing such
/nitric oxide/peroxynitrite and
pathophysiological responses to EMF
exposures: the example of single-
strand DNA breaks
As was noted above, most of the pathophysiological effects of nitric
oxide are mediated through peroxynitrite elevation and consequent
oxidative stress. There are many reviews and other studies, implicat-
ing oxidative stress in generating pathophysiological effects of EMF
exposure [see for example 5764]. In some of these studies, the rise
in oxidative stress markers parallels the rise in nitric oxide, suggest-
ing a peroxynitrite-mediated mechanism [6467].
Peroxynitrite elevation is usually measured through a marker of
peroxynitrite-mediated protein nitration, 3-nitrotyrosine (3-NT). There
are four studies where 3-NT levels were measured before and after
EMF exposure [66, 6870]. Each of these studies provides some evi-
dence supporting the view that EMF exposure increases levels of per-
oxynitrite and therefore 3-NT levels [66, 6870]. Although these
cannot be taken as definitive, when considered along with the evi-
dence on oxidative stress and elevated nitric oxide production in
response to EMF exposure, they strongly suggest a peroxynitrite-
mediated mechanism of oxidative stress in response to EMFs.
ª2013 The Author.
Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
J. Cell. Mol. Med. Vol 17, No 8, 2013
Table 1 EMF responses blocked or lowered by calcium channel blockers
Ref. no. EMF type Calcium channel Cell type or organism Response measured
2 Pulsed magnetic
L-type Human lymphocytes Cell proliferation; cytokine
3 Static magnetic
field (0.1 T)
L-type Human polymorphonuclear
Cell migration; degranulation
5 ELF L-type Rat chromaffin cells Differentiation; catecholamine release
6 Electric field L-type Rat and mouse bone cells Increased Ca
, phospholipase A2, PGE2
7 50 Hz L-type Mytilus (mussel) immunocytes Reduced shape change, cytotoxicity
8 50 Hz L-type AtT20 D16V, mouse pituitary
increase; cell morphology,
premature differentiation
9 50 Hz L-type Neural stem/progenitor cells In vitro differentiation, neurogenesis
10 Static magnetic
L-type Rat Reduction in oedema formation
11 NMR L-type Tumour cells Synergistic effect of EMF on anti-tumour
drug toxicity
12 Static magnetic field L-type Myelomonocytic U937 cells Ca
influx into cells and anti-apoptotic
13 60 Hz L-type Mouse Hyperalgesic response to exposure
14 Single nanosecond
electric pulse
L-type Bovine chromaffin cells Very rapid increase in intracellular Ca
15 Biphasic electric current L-type Human mesenchymal stromal cells Osteoblast differentiation and cytokine
16 DC & AC magnetic
L-type b-cells of pancreas, patch clamped Ca
flux into cells
17 50 Hz L-type Rat pituitary cells Ca
flux into cells
18 50 Hz L-type, N-type Human neuroblastoma IMR32 and
rat pituitary GH3 cells
Anti-apoptotic activity
19 Nanosecond pulse L-type, N-type,
Bovine chromaffin cells Ca
dynamics of cells
20 50 Hz Not determined Rat dorsal root ganglion cells Firing frequency of cells
21 7001100 MHz N-type Stem cellderived neuronal cells Ca
dynamics of cells
22 Very weak electrical
T-type Sharks Detection of very weak magnetic fields
in the ocean
23 Short electric pulses L-type Human eye Effect on electro-oculogram
24 Weak static magnetic
L-type Rabbit Baroreflex sensitivity
25 Weak electric fields T-type Neutrophils Electrical and ion dynamics
26 Static electric fields,
L-type Bovine articular chondrocytes Agrican & type II collagen expression;
calcineurin and other Ca
EMF: electromagnetic field; ELF: extremely low frequency.
960 ª2013 The Author.
Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
Such a peroxynitrite-mediated mechanism may explain the many
studies showing the single-stranded breaks in DNA, as shown by
alkaline comet assays or the similar microgel electrophoresis assay,
following EMF exposures in most such studies [7189], but not in all
[9097]. Some of the factors that are reported to influence whether
such DNA single-strand breaks are detected after EMF exposure
include the type of cell studied [79, 86], dosage of EMF exposure
[78] and the type of EMF exposure studied [73, 77]. Oxidative
stress and free radicals have roles, both because there is a con-
comitant increase in oxidative stress and because antioxidants
have been shown to greatly lower the generation of DNA single-
strand breaks following EMF exposure [72, 75, 81, 82] as has
also been shown for peroxynitrite-mediated DNA breaks produced
under other conditions. It has also been shown that one can block
the generation of DNA single-strand breaks with a nitric oxide
synthase inhibitors [82].
Peroxynitrite has been shown to produce single-strand DNA
breaks [98100], a process that is inhibited by many but not all an-
tioxidants [99, 100]. It can be seen from this that the data on genera-
tion of single-strand DNA breaks, although quite limited, support a
mechanism involving nitric oxide/peroxynitrite/free radical (oxidative
stress). Although the data on the possible role of peroxynitrite in
EMF-induced DNA single-strand breaks are limited, what data are
available supports such a peroxynitrite role.
Discussion and conclusions
How do EMFs composed of low-energy photons produce non-thermal
biological changes, both pathophysiological and, in some cases,
potentially therapeutic, in humans and higher animals? It may be sur-
prising that the answer to this question has been hiding in plain sight
in the scientific literature. However, in this era of highly focused and
highly specialized science, few of us have the time to read the relevant
literature, let alone organize the information found within it in useful
and critical ways.
This study shows that:
1Twenty-three different studies have found that such EMF
exposures act via activation of VGCCs, such that VGCC channel
blockers can prevent responses to such exposures (Table 1).
Most of the studies implicate L-type VGCCs in these responses,
but there are also other studies implicating three other classes
of VGCCs.
2Both extremely low frequency fields, including 50/60 cycle
exposures, and microwave EMF range exposures act via activa-
tion of VGCCs. So do static electric fields, static magnetic fields
and nanosecond pulses.
3Voltage-gated calcium channel stimulation leads to
increased intracellular Ca
, which can act in turn to stimulate
the two calcium/calmodulin-dependent nitric oxide synthases
and increase nitric oxide. It is suggested here that nitric oxide
may act in therapeutic/potentially therapeutic EMF responses
via its main physiological pathway, stimulating cGMP and pro-
tein kinase G. It is also suggested that nitric oxide may act in
pathophysiological responses to EMF exposure, by acting as a
precursor of peroxynitrite, producing both oxidative stress and
free radical breakdown products.
4The interpretation in three above is supported by two spe-
cific well-documented examples of EMF effects. Electromagnetic
fields stimulation of bone growth, modulated through EMF
stimulation of osteoblasts, appears to involve an elevation/nitric
oxide/protein kinase G pathway. In contrast to that, it seems
likely that the EMF induction of single-stranded DNA breaks
involves a Ca
/elevation/nitric oxide/peroxynitrite/free radical
(oxidative stress) pathway.
It may be asked why we have evidence for involvement of VGCCs
in response to EMF exposure, but no similar evidence for involvement
of voltage-gated sodium channels? Perhaps, the reason is that there
are many important biological effects produced in increased intracel-
lular Ca
, including but not limited to nitric oxide elevation, but much
fewer are produced by elevated Na
The possible role of peroxynitrite as opposed to protein kinase G
in producing pathophysiological responses to EMF exposure raises
the question of whether there are practical approaches to avoiding
such responses? Typically peroxynitrite levels can be highly elevated
when both of its precursors, nitric oxide and superoxide, are high.
Consequently, agents that lower nitric oxide synthase activity and
agents that raise superoxide dismutases (SODs, the enzymes that
degrade superoxide) such as phenolics and other Nrf2 activators that
induce SOD activity [101], as well as calcium channel blockers may
be useful. Having said that, this is a complex area, where other
approaches should be considered, as well.
Although the various EMF exposures as well as static electrical
field exposures can act to change the electrical voltage-gradient
across the plasma membrane and may, therefore, be expected to
stimulate VGCCs through their voltage-gated properties, it may be
surprising that static magnetic fields also act to activate VGCCs
because static magnetic fields do not induce electrical changes on
static objects. However, cells are far from static. Such phenomena as
cell ruffling [102,103] may be relevant, where thin cytoplasmic sheets
bounded on both sides by plasma membrane move rapidly. Such
rapid movement of the electrically conducting cytoplasm, may be
expected to influence the electrical charge across the plasma mem-
brane, thus potentially stimulating the VGCCs.
Earlier modelling of electrical effects across plasma membranes
of EMF exposures suggested that such electrical effects were likely to
be too small to explain EMF effects at levels reported to produce bio-
logical changes (see, for example [22]). However, more recent and
presumably more biologically plausible modelling have suggested
that such electrical effects may be much more substantial [104109]
and may, therefore, act to directly stimulate VGCCs.
Direct stimulation of VGCCs by partial depolarization across the
plasma membrane is suggested by the following observations dis-
cussed in this review:
1The very rapid, almost instantaneous increase in intracellular
found in some studies following EMF exposure [8, 16, 17,
19, 21, 27]. The rapidity here means that most, if not all indi-
rect, regulatory effects can be ruled out.
2The fact that not just L-type, but three additional classes of
VGCCs are implicated in generating biological responses to EMF
ª2013 The Author.
Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
J. Cell. Mol. Med. Vol 17, No 8, 2013
exposure (Table 1), suggesting that their voltage-gated proper-
ties may be a key feature in their ability to respond to EMFs.
3Most, if not all, EMF effects are blocked by VGCC channel
blockers (Table 1).
4Modelling of EMF effects on living cells suggests that plasma
membrane voltage changes may have key roles in such effects
[104109]. Saunders and Jefferys stated [110] that ‘It is well
established that electric fields or exposure to low frequency
magnetic fields, will, if of sufficient magnitude, excite nerve tissue
through their interactions with voltage gated ion channels’.
They further state [110] that this is achieved by direct effects on
the electric dipole voltage sensor within the ion channel.
One question that is not answered by any of the available data is
whether what is known as ‘dirty electricity’ [111113], generated by
rapid, in many cases, square wave transients in EMF exposure, also
acts by stimulating VGCCs. Such dirty electricity is inherent in any
digital technology because digital technology is based on the use of
such square wave transients and it may, therefore, be of special con-
cern in this digital era, but there have been no tests of such dirty elec-
tricity that determine whether VGCCs have roles in response to such
fields, to my knowledge. The nanosecond pulses, which are essen-
tially very brief, but high-intensity dirty electricity do act, at least in
part, via VGCC stimulation (Table 1), suggesting that dirty electricity
may do likewise. Clearly, we need direct study of this question.
The only detailed alternative to the mechanism of non-thermal
EMF effects discussed here, to my knowledge, is the hypothesis of
Friedman et al. [114] and supported by Desai et al. [115] where the
apparent initial response to EMF exposure was proposed to be NADH
oxidase activation, leading to oxidative stress and downstream regu-
latory effects. Although they provide some correlative evidence for a
possible role of NADH oxidase [114], the only causal evidence is
based on a presumed specific inhibitor of NADH oxidase, diphenyle-
neiodonium (DPI). However, DPI has been shown to be a non-specific
cation channel blocker [116], clearly showing a lack of such specific-
ity and suggesting that it may act, in part, as a VGCC blocker. Conse-
quently, a causal role for NADH oxidase in responses to EMF
exposure must be considered to be undocumented.
In summary, the non-thermal actions of EMFs composed of low-
energy photons have been a great puzzle, because such photons are
insufficiently energetic to directly influence the chemistry of cells. The
current review provides support for a pathway of the biological action
of ultralow frequency and microwave EMFs, nanosecond pulses and
static electrical or magnetic fields: EMF activation of VGCCs leads to
rapid elevation of intracellular Ca
, nitric oxide and in some cases at
least, peroxynitrite. Potentially therapeutic effects may be mediated
through the Ca
/nitric oxide/cGMP/protein kinase G pathway. Patho-
physiological effects may be mediated through the Ca
/nitric oxide/
peroxynitrite pathway. Other Ca
-mediated effects may have roles as
well, as suggested by Xu et al. [26].
Conflicts of interest
The author confirms that there are no conflicts of interest.
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... Under normal physiological conditions, this voltage sensor controls the opening of the VGCC in the plasma membrane, acting on the partial depolarization response [169]. Four different classes of VGCCs are activated by exposure to ELF-EMF: types L, T, N and types P-Q VGCCs [170]. Channels other than calcium, sodium, potassium and chloride channels are also activated by ELF-EMF exposure. ...
... With ELF-EMF, Ca 2+ channels facilitate the vesicle endocytosis and synaptic plasticity, causing neurotoxicity by activating apoptosis through the mitochondrial pathway, increasing glutamate, GABA and NR2B. Participation of the endoplasmic reticulum has been demonstrated in cells exposed to RF, and different direct and indirect theoretical models that explain from a physical point of view the activation of the channels through voltage sensors have been established [169][170][171][172][173]. Exposure to ELF-MFs increases reactive species causing DNA damage and inhibiting calcineurin [175,176] also due to the effect of PEMF [174]; it also modulates ion channels affecting the ionic conductance of the membrane, the concentration and gene expression of proteins [177]. ...
... All models used to study the interaction between electromagnetic radiation and the immune system of mammals (in vivo or in vitro) show that non-ionizing radiation can activate or reduce the inflammatory response, oxidative stress and can have positive or negative manifestations in COVID-19 disease, depending on the radiation frequency, intensity or modulation and the exposure time. 2. Intracellular calcium entry can also be modulated by beneficial or adverse effects of EMF on inflammation and/or cell death [170]. Both sides of the coin [179] must also be taken into account in regard to progression to severe COVID-19 disease (Figure 1). ...
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Programmed cell death constitutes a fundamental part of the immune response to viral infection. This process forms part of the host defence mechanism and also enables establishment of biomarkers of disease severity. Natural or anthropogenic sources of microwaves emit energy and may alter the ecology of the COVID-19 virus in the environment. Determining the associated effects on the immune system and on the health of hosts with COVID-19 disease is thus important. In this review paper, we consider studies analyzing the influence of electromagnetic fields on innate and acquired immune responses in humans, and above all on preclinical experimental animal models and in vitro models, and we also consider studies analyzing immunity acquired from COVID-19 infections associated with cell death. We focus on the effects of electromagnetic fields and the influence of oxidative stress on stimulation or immunomodulation, the inflammatory response, autoimmunity and the participation of intracellular calcium channels in the immunology of COVID-19 disease. Non-ionizing radiation can activate or reduce the inflammatory response, oxidative stress and the entry of intracellular calcium and can facilitate or reduce cell death. The review of experimental study findings indicates that exposure to non-ionizing radiation can also have a bidirectional effect on the immune system, either slowing down or enhancing the processes that lead to the cell death associated with COVID-19 disease.
... Responsible for the response to electrical stimulation are the voltage-gated calcium channels [29,31]. These allow the entry of extracellular calcium following stimulation, which then acts as a second messenger internally, activating signal transduction and regulating a series of essential functions [32][33][34]. ...
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In the tissue regeneration field, stem cell transplantation and the control of their differentiation represent a promising therapeutic strategy. The second aspect can be achieved using electrical stimulation. This study aims to characterize the effect of a microsecond electrical stimulation on MSCs and iNSCs, in the context of the RISEUP FET-OPEN project (n. 964562) that seeks to control these cells differentiation for the spinal cord injury treatments. Here, the effect of a specific microsecond electric pulses stimulation, characterized by bipolar pulses of 100 µs + 100 µs, delivered for 30 minutes at an intensity of 250 V/cm, on i) cell proliferation, ii) cell cycle, iii) gene expression and iv) apoptosis was evaluated. Results show that the stimulation does not affect cell proliferation, cell cycle, and apoptosis, but induced some variations in gene expression, in particular in EGR1, FOS, and POU5F1. These ob-servations led us to deeply investigate the cell proliferation until 72h from the stimulation observing an increase in the iNSCs. The main outcome of this study is that the chosen stimulation protocol is safe and not toxic for MSCs and iNSCs. The observed variations in the gene expression need to be deeply investigated to assess the molecular mechanisms involved.
... (1) La fuerza de contracción del miocardio, depende en gran medida de la concentración de los iones de calcio en los líquidos extracelulares. (5) Después de la exposición a CEM-FEB existe un aumento inmediato del calcio intracelular, (6) lo que, a nivel de las células de la musculatura lisa de los vasos sanguíneos, puede ser favorecedor de las acciones constrictivas. Se ha considerado que la exposición a CEM-FEB puede afectar el corazón. ...
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Introducción: La generación de energía eléctrica constituye uno de los indicadores más importantes de desarrollo de una nación. En ese proceso se generan campos electromagnéticos de frecuencia extremadamente baja, que pudieran afectar el corazón. Objetivo: Identificar la asociación entre el riesgo cardiovascular y la exposición a los campos electromagnéticos de frecuencia extremadamente baja. Métodos: Se realizó un estudio transversal, descriptivo en el Área de Salud 27 de Noviembre, del municipio Marianao de la provincia La Habana, en el año 2018. La muestra estuvo constituida por 152 individuos. Se les determinó el riesgo cardiovascular, según las tablas predictivas de Gaziano sin laboratorio. Se realizaron mediciones de las densidades de flujo magnético en sus viviendas. Se valoró si estas, se asociaron a la intensidad de generación de electricidad de la vecina central termoeléctrica y con el riesgo cardiovascular global de los residentes. Se utilizó correlación no paramétrica de Spearman. Resultados: El 31,6 % de la población estudiada fue evaluada con el riesgo cardiovascular alto y muy alto en su conjunto. 120 individuos estuvieron expuestos en sus viviendas a densidades del flujo magnético entre 0 y 0,9 µT. Existió una correlación estadística significativa, entre la intensidad de la corriente generada por la industria y las densidades de flujo magnético en las habitaciones usadas para dormir. Conclusiones: No se observó asociación entre el riesgo cardiovascular y las densidades de flujo magnético medidas en las viviendas. La exposición a los campos electromagnéticos de frecuencia extremadamente baja no constituyó un factor de riesgo cardiovascular para la población estudiada.
... Their pilot study suggests that the EMF treatment protocol has clinical relevance and can be used safely and effectively [21]. Pall concluded that the direct effect of extremely low frequency electromagnetic fields can be attributed to phenomena brought about by the activation of calcium channels and membrane transport processes, as well as increased enzyme activity [22]. In clinical trials involving the elderly with the use of a pulsed electromagnetic field, Iannitti et al. reported significant benefits in the form of reduced joint pain and stiffness, as well as improved physical performance [23]. ...
Full-text available
Background. Bell’s palsy is a spontaneous paralysis of the facial nerve (i.e. cranial nerve VII). It presents with muscle weakness leading to facial asymmetry, with a drooping corner of the mouth, loss of the ability to whistle, blink, close the eyelid, purse lips or grin. The forehead on the affected side becomes smooth and the patient is not able to frown or raise eyebrows. Objective. The aim of the study was to evaluate the effect of combined electrophysical and physiotherapeutic methods on accelerating recovery from facial nerve palsy. Material and Methods. The authors describe two cases of Bell’s palsy, treated with simulta-neous application of electrophysical agents, in the form of an extremely low-frequency elec-tromagnetic field (ELF-EMF) and high-energy LED light, and physiotherapy modalities, i.e. proprioceptive neuromuscular facilitation (PNF) and kinesiotaping (KT). Results. After four weeks of electrophysical and physiotherapeutic treatments, a fully satis-factory and stable therapeutic effect was achieved. Conclusions. The interdisciplinary therapy using ELF-EMF + LED combined with PNF and KT treatments proved to be effective in accelerating recovery from facial nerve palsy. Further studies are needed to establish appropriate protocols.
In order to provide context and help for newcomers in the area of biological physics, the goal of this chapter is to develop a feeling for the physics of cell membranes. Our aim is to present our interpretation of EMB in a language familiar to physicists. In practice, most of the attention will be focused at the cellular level, focusing on the electrical and mechanical properties of membranes. Thus, we begin with a brief overview of the basic morphological characteristics of the membrane enveloping living cells which separates the cytoplasmic medium (cytosol) from the extracellular medium. Since we are interested in the ED and EP mechanisms we first place an emphasis on the electrical properties of membranes. We outline the interpretation of typical cell membrane electrical measurements and show how this allows a basic introduction into the mechanisms underlying ED and EP. Since perturbations to the mechanical environment can affect cell behavior and its normal physiology, we next briefly review the current understanding of how the mechanical characteristics of cell relate to underlying architectural changes and describe how these changes evolve with membrane deformability in response to an applied stress. The chapter closes with a discussion of possible generalizations to cell assemblies and simple models of biological tissues.
Despite encouraging advances in early diagnosis and treatment, cardiovascular diseases (CVDs) remained a leading cause of morbidity and mortality worldwide. Increasing evidence has shown that the electromagnetic field (EMF) influences many biological processes, which has attracted much attention for its potential therapeutic and diagnostic modalities in multiple diseases, such as musculoskeletal disorders and neurodegenerative diseases. Nonionizing EMF has been studied as a therapeutic or diagnostic tool in CVDs. In this review, we summarize the current literature ranging from in vitro to clinical studies focusing on the therapeutic potential (external EMF) and diagnostic potential (internal EMF generated from the heart) of EMF in CVDs. First, we provided an overview of the therapeutic potential of EMF and associated mechanisms in the context of CVDs, including cardiac arrhythmia, myocardial ischemia, atherosclerosis, and hypertension. Furthermore, we investigated the diagnostic and predictive value of magnetocardiography in CVDs. Finally, we discussed the critical steps necessary to translate this promising approach into clinical practice.
Conference Paper
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Living organisms of Saccharomyces cerevisiae are subjected to extremely low-frequency electromagnetic field exposition during the workweek, followed by cultivation over the weekend. Initially, the weight of the inoculum with YPD agar is examined in the exposure setup without exposition between the first and the last day. Subsequently, the coil is supplied, generating a static and time-varying electromagnetic field. The theoretical assumption underlying this experiment is based on the modified ion parametric resonance theory, which specifically focuses on calcium ions at a frequency of 192.26 Hz. The time-varying magnetic field amplitude is set at 451.66 μT, accompanied by a static field of 250.92 μT. By employing an experimental protocol, the cells are exposed to these conditions for a long-term exposition within Petri dishes.
Microcurrent therapy is a form of therapy that uses Galvanic, direct current (DC) with low amperage (<1000 μA) and low frequency (0.5–100 Hz) for healing purposes. Microcurrent therapy simply produces electrical signals like those naturally produced in the body during repair and healing process.KeywordsMagnetic fieldInjured tissuePulse magnetic fieldPulse electromagnetic fieldPotassium pump
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During the past decade considerable evidence has accumulated demonstrating that nonthermal exposures of cells of the immune system to extremely low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes that might be relevant to in vivo immune activity. A similar responsiveness to nonionizing electromagnetic energy in this frequency range has also been documented for tissues of the neuroendocrine and musculoskeletal system. However, knowledge about the underlying biological mechanisms by which such fields can induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca(2+)-regulated activity is involved in bioactive ELF field coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells and then closely examines new results that suggest a role for Ca2+ in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca2+ signaling processes are involved in the mediation of field effects on the immune system.
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Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system.
Peroxynitrite decay in weakly alkaline media occurs by two concurrent sets of pathways which are distinguished by their reaction products. One set leads to net isomerization to NO3- and the other set to net decomposition to O-2 plus NO2-. At sufficiently high peroxynitrite concentrations, the decay half-time becomes concentration-independent and approaches a limiting value predicted by a mechanism in which reaction is initiated by unimolecular homolysis of the peroxo, O-O bond, i.e., the following reaction: ONOOH --> (OH)-O-. + (NO2)-N-.. This dynamical behavior excludes alternative postulated mechanisms that ascribe decomposition to bond rearrangement within bimolecular adducts. Nitrate and nitrite product distributions measured at very low peroxynitrite concentrations also correspond to predictions of the homolysis model, contrary to a recent report from another laboratory. Additionally, (1) the rate constant for the reaction ONOO- --> (NO)-N-. + O-.(2), which is critical to the kinetic model, has been confirmed, (2) the apparent volume of activation for ONOOH decay (DeltaV(double dagger) = 9.7 +/- 1.4 cm(3)/mol) has been shown to be independent of the concentration of added nitrite and identical to most other reported values, and (3) complex patterns of inhibition of O-2 formation by radical scavengers, which are impossible to rationalize by alternative proposed reaction schemes, are shown to be quantitatively in accord with the homolysis model. These observations resolve major disputes over experimental data existing in the literature; despite extensive investigation of these reactions, no verifiable experimental evidence has been advanced that contradicts the homolysis model.
Electric and electromagnetic fields are, collectively, one form of biophysical technique which regulate extracellular matrix (ECM) synthesis and may be useful in clinically stimulating repair of fractures and nonunions. Preclinical studies have shown that electric and electromagnetic fields regulate proteoglycan (PG) and collagen synthesis in models of endochondral ossification, and increase bone formation in vivo and in vitro. A substantial number of clinical studies have been done that suggest acceleration of bone formation and healing, particularly osteotomies and spine fusions, by electric and electromagnetic fields. Many of these studies have used randomized, placebo controlled designs. In osteotomy trials, greater bone density, trabecular maturation, and radiographic healing were observed in actively treated, compared with placebotreated patients. In spine fusions, average union rates of 80% to 90% were observed in actively treated patients across numerous studies compared with 65% to 75% in placebo-treated patients. Uncontrolled, longitudinal cohort studies of delayed and nonunions report mean union rates of approximately 75% to 85% in fractures previously refractory to healing. The few randomized controlled studies in delayed and nonunions suggest improved results with electric and electromagnetic fields compared with placebo treatment, and equivalent to bone grafts. Am J Orthop. 2004 Jan;33(1):27-30
The total current of Ca{sup 2+} ions through patch-clamped cell membranes was measured while exposing clonal insulin-producing β-cells (RINm5F) to a combination of DC and AC magnetic fields at so-called cyclotron resonance conditions. Previous experimental evidence supports the theory that a resonant interaction between magnetic fields and organisms can exist. This experiment was designed to test one possible site of interaction: channels in the cell membrane. The transport of Ca{sup 2+} ions through the protein channels of the plasma membrane did not show any resonant behavior in the frequency range studied.
Purpose: To investigate the effects of 12kV/m electric (E) field sourced by power lines on oxidative and nitrosative stress, and antioxidant status. Furthermore, the study aimed to examine the protective effects of N-Acetyl-L-cysteine (NAC) and epigallocatechin-gallate (EGCG) in the liver tissues of guinea pigs against the possible detriments of electromagnetic field exposure. Materials and methods: Guinea pigs were exposed to 50Hz 12kV/m E-field. NAC and EGCG were administerated intraperitoneally. Malonedialdehyde (MDA), a product of lipid peroxidation (LPO), and nitric oxide derivatives (nitrate (NO(3)), nitrite (NO(2)), total level of nitric oxide (NO(x)) were estimated as biomarkers of oxidative and nitrosative stress, respectively. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and myeloperoxidase (MPO) were evaluated as endogenous antioxidant enzymes in liver tissues of the guinea pigs. Results: The results of our study indicated a significant increase in the levels of oxidant products (MDA, NO(3), NO(2), NO(x)), and a significant decrease in antioxidant enzyme (SOD, GSH-Px and MPO) activities. We also found that the individual or plus application of NAC and EGCG resulted in the reduction of oxidative stress prior to E field application. Conclusion: To conclude, extremely low frequency (ELF) electric field has potential harmful effects on the living organisms by enhancing the free radical production. NAC and EGCG might have hepatoprotective effects in ELF-E field induced oxidative and nitrosative stress.
This study shows that a non-thermal pulse-modulated RF signal (PRF), configured to modulate calmodulin (CaM) activation via acceleration of Ca(2+) binding kinetics, produced an immediate nearly 3-fold increase in nitric oxide (NO) from dopaminergic MN9D cultures (P<0.001). NO was measured electrochemically in real-time using a NO selective membrane electrode, which showed the PRF effect occurred within the first seconds after lipopolysaccharide (LPS) challenge. Further support that the site of action of PRF involves CaM is provided in human fibroblast cultures challenged with low serum and exposed for 15min to the identical PRF signal. In this case a CaM antagonist W-7 could be added to the culture 3h prior to PRF exposure. Those results showed the PRF signal produced nearly a two-fold increase in NO, which could be blocked by W-7 (P<0.001). To the authors' knowledge this is the first report of a real-time effect of non-thermal electromagnetic fields (EMF) on NO release from challenged cells. The results provide mechanistic support for the many reported bioeffects of EMF in which NO plays a role. Thus, in a typical clinical application for acute post operative pain, or chronic pain from, e.g., osteoarthritis, EMF therapy could be employed to modulate the dynamics of NO via Ca/CaM-dependent constitutive nitric oxide synthase (cNOS) in the target tissue. This, in turn, would modulate the dynamics of the signaling pathways the body uses in response to the various phases of healing after physical or chemical insult or injury.