Correlation of magnetic AC field on cardiac myocyte Ca2+ transients at different magnetic DC levels

The purpose of this study was to determine the effect of extremely low frequency and weak magnetic fields (WMF) on cardiac myocyte Ca²⁺ transients, and to explore the involvement of potassium channels under the WMF effect. In addition, we aimed to find a physical explanation for the effect of WMF on cardiac myocyte Ca²⁺ transients. Indo‐1 loaded cells, which were exposed to a WMF at 16 Hz and 40 nT, demonstrated a 75 ± 4% reduction in cytosolic Ca²⁺ transients versus control. Treatment with the K_ATP channel blocker, glibenclamide, followed by WMF at 16 Hz exposure, blocked the reduction in cytosolic calcium transients while treatment with pinacidil, a K_ATP channel opener, or chromanol 293B, a selective potassium channel blocker of the delayed rectifier K⁺ channels, did not inhibit the effect. Based on these finding and the ion cyclotron resonance frequency theory, we further investigated the effect of WMF by changing the direct current (DC) magnetic field (B₀). When operating different DC magnetic fields we showed that the WMF value changed correspondingly: for B₀ = 44.5 µT, the effect was observed at 17.05 Hz; for B₀ = 46.5 µT, the effect was observed at 18.15 Hz; and for B₀ = 49 µT the effect was observed at 19.1 Hz. We can conclude that the effect of WMF on Ca²⁺ transients depends on the DC magnetic field level. Bioelectromagnetics 33:634–640, 2012. © 2012 Wiley Periodicals, Inc.     

A Lorentz model for weak magnetic field bioeffects: Part II—Secondary transduction mechanisms and measures of reactivity

In Part I it was shown that the thermal component of the motion of a charged particle in an oscillator potential, that is, within a molecular binding site, rotates at the Larmor frequency in an applied magnetic field. It was also shown that the Larmor angular frequency is independent of the thermal noise strength and thus offers a mechanism for the biological detection of weak (µT‐range) magnetic fields. Part II addresses the question of how the Larmor trajectory could affect biological reactivity. The projection of the motion onto a Cartesian axis measures the nonuniformity of the Larmor trajectory in AC and combined AC/DC magnetic fields, suggesting a means of assessing resonances. A physically meaningful measure of reactivity based upon the classical oscillator trajectory is suggested, and the problem of initial conditions is addressed through averaging over AC phases. AC resonance frequencies occur at the Larmor frequency and at other frequencies, and are dependent upon the ratio of AC/DC amplitudes and target kinetics via binding lifetime. The model is compared with experimental data reported for a test of the ion parametric resonance (IPR) model on data from Ca²⁺ flux in membrane vesicles, neurite outgrowth from PC‐12 cells and a cell‐free calmodulin‐dependent myosin phosphorylation system, and suggests Mg²⁺ is the target for these systems. The results do not require multiple‐ion targets, selection of isotopes, or additional curve fitting. The sole fitting parameter is the binding lifetime of the target system and the results shown are consistent with the literature on binding kinetics. Bioelectromagnetics 30:476–488, 2009. © 2009 Wiley‐Liss, Inc.     

Intracellular calcium oscillations induced in a T-cell line by a weak 50 Hz magnetic field

Applied weak magnetic fields have been shown to affect cellular activity on several levels, but the mechanisms involved remain elusive. We have decided to study an early signal transduction event in the human T cell line Jurkat; oscillations of free [Ca²⁺]i, of the type seen by crosslinking the CD3 complex. Cells were exposed to a 50 Hz, 0.1 mT, sinusoidal magnetic field while intracellular free calcium was measured in individual cells, using fura-2 as a probe. An acute response was observed with oscillatory increases in [Ca²⁺]i, which subsided when the field was turned off. The effect of the magnetic field on [Ca²⁺]i was comparable to that achieved by an anti-CD3 monoclonal antibody. © 1993 Wiley-Liss, Inc.     

Stimulation of Ca2+ influx in rat pituitary cells under exposure to a 50 Hz magnetic field

The effect of exposure of single rat pituitary cells to 50 Hz sine wave magnetic fields of various strengths on the intracellular free Ca²⁺ concentration ([Ca²⁺]_i) was studied by using dual-emission microfluorimetry, using indo-1 as probe. A 30 min exposure of the cells to vertical 50 μT peak magnetic field triggered a long-lasting increase in [Ca²⁺]_i from a basal value of about 185 ± 4 nM to 326 ± 41 nM (S.E.; n = 150). The vertical and horizontal components of the static magnetic field were 57 and 15 μT, respectively. The 50 Hz ambient magnetic field was always below 0.1 μT rms. The effect was observed both at 25 ± 2 °C and at 37 ± 2 °C. Responsive cells, for which [Ca²⁺]_i rose to values above 309 nM, were identified as lactotrophs and represented 29% of the total pituitaries. [Ca²⁺]_i increase, for the most part, was due to Ca²⁺ influx through voltage-dependent dihydropiridine-sensitive calcium channels inhibited by PN 200-110. However, neither Ca²⁺ channel blockers nor removal of Ca²⁺ from the external medium during exposure completely prevented the field-induced [Ca²⁺]_i increase. Additional experiments using an MTT colorimetric assay showed that alteration of Ca²⁺ homeostasis of lactotrophs was associated with impairment of some mitochondrial processes. © Wiley-Liss, Inc.     

Modulation of Ca2+ dependent protease activity in fish and invertebrates by weak low-frequency magnetic fields

Results of experiments addressing the effects of weak low-frequency magnetic fields on intracellular Ca²⁺ dependent proteinases (calpains) from invertebrates and fish are discussed. Exposure of live animals to weak low-frequency magnetic fields with parameters chosen to induce the resonance of Ca²⁺ ions led to a significant decrease of calpain activity in the animals investigated. The physical factor studied also caused partial loss of activity in preparations of Ca²⁺ dependent proteinases obtained from invertebrates and fish. The phenomenon discovered is in accordance with the interference model of the effect of weak low-frequency magnetic fields on biological objects.     

Effects and molecular mechanisms of the biological action of weak and extremely weak magnetic fields

A number of effects of weak combined (static and alternating) magnetic fields with an alternating component of tens and hundreds nT at a collinear static field of 42 μT, which is equivalent to the geomagnetic field, have been found: activation of fission and regeneration of planarians Dugesia tigrina, inhibition of the growth of the Ehrlich ascites carcinoma in mice, stimulation of the production of the tumor necrosis factor by macrophages, decrease in the protection of chromatin against the action of DNase 1, and enhancement of protein hydrolysis in systems in vivo and in vitro. The frequency and amplitude ranges for the alternating component of weak combined magnetic fields have been determined at which it affects various biological systems. Thus, the optimal amplitude at a frequency of 4.4 Hz is 100 nT (effective value); at a frequency of 16.5 Hz, the range of effective amplitudes is broader, 150–300 nT; and at a frequency of 1 (0.5) Hz, it is 300 nT. The sum of close frequencies (e.g., 16 and 17 Hz) produces a similar biological effect as the product of the modulating (0.5 Hz) and carrying frequencies (16.5 Hz), which is explained by the ratio A = A ₀sinω₁ t + A ₀sinω₂ t = 2A ₀sin(ω₁ + ω₂)t/2cos(ω₁–ω₂)t/2. The efficiency of magnetic signals with pulsations (the sum of close frequencies) is more pronounced than that of sinusoidal frequencies. These data may indicate the presence of several receptors of weak magnetic fields in biological systems and, as a consequence, a higher efficiency of the effect at the simultaneous adjustment to these frequencies by the field. Even with consideration of these facts, the mechanism of the biological action of weak combined magnetic fields remains still poorly understood.     

Ca2+ ion transport through patch-clamped cells exposed to magnetic fields

The total current of Ca²⁺ 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 Ca²⁺ ions through the protein channels of the plasma membrane did not show any resonant behavior in the frequency range studied. © 1995 Wiley-Liss, Inc.     

Intracellular calcium oscillations in a T-cell line after exposure to extremely-low-frequency magnetic fields with variable frequencies and flux densities

Low-frequency magnetic fields (MF) can increase the cytosolic calcium concentration ([Ca²⁺]_i) in lymphocytes in the same manner as a physiological stimulus such as antibodies directed towards the CD3 complex. In this study, MF with various frequencies and flux densities were used, while [Ca²⁺]_i changes were recorded using microfluorometry with fura-2 as a probe. The applied sinusoidal MF induced oscillatory changes of [Ca²⁺], in the leukemic cell line Jurkat in a manner similar to that seen with stimulation by antibodies. The response at 0.15 mT was over a frequency range from 5 to 100 Hz, with a fairly broad peak having its maximum at 50 Hz. The result of testing increasing flux densities at 50 Hz was a threshold response with no effect below 0.04 mT and a plateau at 0.15 mT. On the basis of the characteristic calcium pattern resulting from an applied MF, we suggest that MF influence molecular events in regular signal transduction pathways of T cells. © 1995 Wiley-Liss, Inc.     

Environmental magnetic fields inhibit the antiproliferative action of tamoxifen and melatonin in a human breast cancer cell line

We have previously reported that environmental-level magnetic fields (1.2 μT [12 milligauss], 60 Hz) block the growth inhibition of the hormone melatonin (10⁻⁹ M) on MCF-7 human breast cancer cells in vitro. We now report that the same 1.2 μT, 60 Hz magnetic fields significantly block the growth inhibitory action of pharmacological levels of tamoxifen (10⁻⁷ M). In biophysical studies we have taken advantage of Faraday's Law of Current Induction and tested whether the 1.2 μT magnetic field or the associated induced electric field is responsible for this field effect on melatonin and tamoxifen. We observe that the magnetic field component is associated with the field blocking effect on melatonin and tamoxifen function. To our knowledge the tamoxifen studies represent the first experimental evidence for an environmental-level magnetic field modification of drug interaction with human breast cancer cells. Together, these findings provide support to the theory that environmental-level magnetic fields can act to modify the action of a drug or hormone on regulation of cell proliferation. Melatonin and tamoxifen may act through different biological pathways to down-regulate cell growth, and further studies are required to identify a specific biological site of interaction for the 1.2 μT magnetic field. Bioelectromagnetics 18:555–562, 1997. Published 1997 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Serum plays a critical role in modulating [Ca2+]c of primary culture bone cells exposed to weak ion-resonance magnetic fields

Primary-culture bone cells were exposed to ion-resonance (IR) magnetic fields tuned to Ca²⁺. Cytosolic calcium concentration, [Ca²⁺]_c, was measured by using fura-2 during field exposure. The fields investigated were 20 μT static + 40 μT p-p at either 15.3 or 76.6 Hz, and 0.13 mT static + either 0.5 or 1.0 mT p-p at 100 Hz. Other parameters included field orientation, culture age (2 or 5 days after plating), and the presence of serum (0 or 2%) during exposure. Total experiment time was 29.5 min: The field was applied after 2 min, and bradykinin was added as an agonist control after 22 min. The data were quantified on a single-cell basis during the 2–22 min exposure period in terms of the magnitude of the largest occurring [Ca²⁺]_c spike normalized to local baseline. Field-exposed and control groups were characterized in terms of the percent of cells exhibiting spike magnitudes above thresholds of 100 or 66% over baseline and were compared by using Fisher's exact test. Without serum, there was little evidence that IR magnetic fields altered [Ca²⁺]_c. However, in the presence of 2% serum, 3 of the 16 experiments exhibited significant effects at the 100% threshold. Reducing this threshold to 66% resulted in five experiments exhibiting significant effects. Most strikingly, in all of these cases, the field acted to enhance [Ca²⁺]_c activity as opposed to suppressing [Ca²⁺]_c activity. These findings suggest a role for serum or for constituents within serum in mediating the effects of IR magnetic fields on cells and may provide a resolution pathway to the dilemma imposed by theoretical arguments regarding the possibility of such phenomena. Possible roles of serum and future studies are discussed. Bioelectromagnetics 18:203–214, 1997. © 1997 Wiley-Liss, Inc.     

Interaction between weak low frequency magnetic fields and cell membranes

The question of whether very weak low frequency magnetic fields can affect biological systems, has attracted attention by many research groups for quite some time. Still, today, the theoretical possibility of such an interaction is often questioned and the site of interaction in the cell is unknown. In the present study, the influence of extremely low frequency (ELF) magnetic fields on the transport of Ca(2+) was studied in a biological system consisting of highly purified plasma membrane vesicles. We tested two quantum mechanical theoretical models that assume that biologically active ions can be bound to a channel protein and influence the opening state of the channel. Vesicles were exposed for 30 min at 32 degrees C and the calcium efflux was studied using radioactive (45)Ca as a tracer. Static magnetic fields ranging from 27 to 37 micro T and time varying magnetic fields with frequencies between 7 and 72 Hz and amplitudes between 13 and 114 micro T (peak) were used. We show that suitable combinations of static and time varying magnetic fields directly interact with the Ca(2+) channel protein in the cell membrane, and we could quantitatively confirm the model proposed by Blanchard.     

Effect of weak combined magnetic fields on the metamorphosis of the mealworm beetle Tenebrio molitor

The effects of weak combined magnetic fields adjusted to the parametric resonance for Ca²⁺ and K⁺ and extremely weak alternating magnetic field on the metamorphosis of the mealworm beetle Tenebrio molitor have been studied. It was shown that the exposure of pupas of insects to all above-indicated types of fields stimulates the metamorphosis. However, after the exposure to weak combined magnetic fields adjusted to the parametric resonance for Ca²⁺ and K⁺, the number of insects with anomalies increases, which is not observed by the action of the weak alternating magnetic field.     

Effects of extremely-low-frequency magnetic fields on biological magnetite

Adair [Bioelectromagnetics 14:1–4, 1993] writes that “the effects of 60 Hz magnetic fields of 5 μT (50 mG) or less on biological structures holding magnetite (Fe₃O₄) are shown to be much smaller than those from thermal agitation; hence such interactions cannot be expected to be biologically significant.” This conclusion is questioned, because it appears to be based on a model that probably has very limited validity for pertinent biological systems. Furthermore, biologically plausible parameters can be selected to show that even this particular model does not exclude biologically significant effects of 60 Hz magnetic fields below 5 μT. Reported experimental results indicate effects in mammals of 50 Hz fields at the 1 μT level. © 1994 Wiley-Liss, Inc.     

The effect of weak magnetic fields on the chemiluminescence of human blood

Exposure of heparinized human venous blood that was diluted with a phosphate buffer to a combination of a static magnetic field (42 µT) and a weak (amplitude range 108–3440 nT) variable low-frequency (1, 4.4, and 16.5 Hz, ratio of amplitudes 6: 1: 1.6, respectively) magnetic field collinear to the static magnetic field enhanced blood chemiluminescence that was induced by the addition of luminol or lucigenin at physiological temperature. The free-radical scavenger edaravone (MCI-186) and apocynin, an inhibitor of NADPH oxidase, reduced the intensity of blood chemiluminescence and alleviated the effects of the magnetic fields.     

Origins of electromagnetic hypersensitivity to 60 Hz magnetic fields: A provocation study

With increasing electrical device usage, social concerns about the possible effects of 60 Hz electromagnetic fields on human health have increased. The number of people with self‐attributed electromagnetic hypersensitivity (EHS) who complain of various subjective symptoms such as headache and insomnia has also increased. However, it is unclear whether EHS results from physiological or other origins. In this double‐blinded study, we simultaneously investigated physiological changes (heart rate, respiration rate, and heart rate variability), subjective symptoms, and perception of the magnetic field to assess origins of the subjective symptoms. Two volunteer groups of 15 self‐reported EHS and 16 non‐EHS individuals were tested with exposure to sham and real (60 Hz, 12.5 µT) magnetic fields for 30 min. Magnetic field exposure did not have any effects on physiological parameters or eight subjective symptoms in either group. There was also no evidence that the EHS group perceived the magnetic field better than the non‐EHS group. In conclusion, the subjective symptoms did not result from the 60 Hz, 12.5 µT magnetic field exposures but from other non‐physiological factors. Bioelectromagnetics 33:326–333, 2012. © 2011 Wiley Periodicals, Inc.     

The role of hydroxyl radicals and calcium ions in the priming of a respiratory burst in neutrophils and the increase in luminol-dependent blood chemiluminescence on exposure to combined magnetic fields with a very weak low-frequency alternating component

The intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA AM) used at low concentrations (1.0 and 2.5 μM) was shown to block the priming effect of weak combined static (42 μT) and low-frequency collinear alternating (1.0, 4.4, and 16.5 Hz; 0.86 μT) magnetic fields. This blockage was inferred from a greater increase in chemiluminescence observed for a mouse neutrophil suspension exposed to combined magnetic fields in response to the bacterial peptide N-formyl–Met–Leu–Phe added in the presence of luminol. Similar results were obtained for the effect of BAPTA AM on luminol-dependent chemiluminescence of whole blood. The priming effect of weak combined magnetic fields on the respiratory burst in neutrophils did not depend on the presence of extracellular Ca²⁺ and was not affected by the hydroxyl radical scavenger dimethyl sulfoxide used at 0.025–1.0 mM.     

Effects of extremely-law-frequency electromagnetic fields on ion transport in several mammalian cells

We have investigated the effects of sinusoidal electromagnetic fields (EMF) on ion transport (Ca²⁺, Na⁺, K⁺, and H⁺) in several cell types (red blood cells, thymocytes, Ehrlich ascites tumor cells, and HL60 and U937 human leukemia cells). The effects on the uptake of radioactive tracers as well as on the cytosolic Ca²⁺ concentration ([Ca²⁺]_i), the intracellular pH (pH_i), and the transmembrane potentsial (TMP) were studied. Exposure to EMF at 50 Hz and 100–2000 μT (rms) had no significant effects on any of these parameters. Exposure to EMF of 20–1200 μT (rms) at the estimated cyclotron magnetic resonance frequencies for the respective ions had no significant effects except for a 12–32% increase of the uptake of ⁴²K within a window at 14.5–15.5 Hz and 100–200 μT (rms), which was found in U937 and Ehrlich cells but not in the other cell types. © 1994 Wiley-Liss, Inc.     

Sine Wave Extremely Low Frequency Magnetic Fields Protect Chick Embryos Against UV-Induced Death

Four-day-old chicken embryos were exposed to extremely low frequency (ELF) magnetic fields (MF) prior to UV exposure (75 min, predominantly UV-C, 0.4 mW/cm²) to investigate possible MF-mediated protection against lethal effects of UV. The UV exposure typically resulted in a 20% survival rate (as judged by beating hearts) in sham-exposed embryos 3 h postexposure. In contrast, exposure to a 50 (10, 50, or 100 µT) or 60 Hz (10 µT) vertical MF caused a significant increase in survival rate, observed only 30 min after UV exposure. No difference in protection levels was seen between these exposure intensities. A horizontal 50 Hz MF (10, 50, or 100 µT) did not result in the general protection against UV-induced death observed for vertical fields, suggesting that the size of the induced electric field (which differs between horizontal and vertical exposure) is important for the MF-induced protection. To explore the molecular mechanisms involved in this effect, immunoblotting experiments with an antibody against the inducible form of hsp70 were performed. These showed that application of MF (50 Hz, 200 µT, 1 h) induced hsp70 expression in human K562 cells.     

Delayed consequences of extremely low‐frequency magnetic fields and the influence of adverse environmental conditions on roach Rutilus rutilus embryos

This study presents data collected over a 6 year period on the effects of extremely low‐frequency magnetic fields (MFs) (1·4–1·6 µT, 500 Hz and 1·4–1·6 µT, 72·5 Hz) and MFs in combination with other environmental stressors (elevated temperature, 0·01 mg l^?1 trichlorfon, 0·01 mg l^?1 copper sulphate pentahydrate) on roach Rutilus rutilus embryos. Effects were studied during different stages of early development. Rutilus rutilus were raised in ponds for 4 months after exposure to MFs. The mass, standard length (L_S) and morphological characteristics of underyearlings which were exposed as embryos were recorded. An increase in embryo mortality and a decrease in L_S and mass indices in underyearlings were noted after they had been exposed to a combination of MFs and different adverse environmental factors. In addition, exposure to MFs led to changes in the total number of vertebrae and the number of seismosensory system openings in the mandibular bones of underyearlings. MFs of different frequency caused both increases (500 Hz) and decreases (72·5 Hz) in morphological diversity. The stressors used in this study, however, did not increase the fluctuating asymmetry of bilateral morphological characteristics. The possible microevolutionary effects of exposure to MFs alone and in combination with other adverse environmental factors upon natural fish populations are discussed.     

Behavioural evidence that magnetic field effects in the land snail,Cepaea nemoralis,might not depend on magnetite or induced electric currents

Although extremely low frequency (ELF) magnetic fields (<300 Hz) appear to exert a variety of biological effects, the magnetic field sensing/transduction mechanism(s) remains to be established. Here, using the inhibitory effects of magnetic fields on endogenous opioid peptide-mediated “analgaesic” response of the land snail. Cepaea nemoralis, we addressed the mechanism(s) of action of ELF magnetic fields. Indirect mechanisms involving both induced electric fields and direct magnetic field detection mechanisms (e.g., magnetite, parametric resonance) were evaluated. Snails were exposed to a static magnetic field (B_DC=78±1 μT) and to a 60 Hz magnetic field (B_AC=299±1 μT peak) with the angle between the static and 60 Hz magnetic fields varied in eight steps between 0° and 90°. At 0° and 90°, the magnetic field reduced opioid-induced analgaesia by approximately 20%, and this inhibition was increased to a maximum of 50% when the angle was between 50° and 70°. Because B_AC was fixed in amplitude, direction, and frequency, any induced electric currents would be constant independent of the B_AC/B_DC angle. Also, an energy transduction mechanism involving magnetite should show greatest sensitivity at 90°. Therefore, the energy transduction mechanism probably does not involve induced electric currents or magnetite. Rather, our results suggest a direct magnetic field detection mechanism consistent with the parametric resonance model proposed by Lednev. © 1996 Wiley-Liss, Inc.