In the present study, Panagopoulos and Yakymenko et al. provide an updated description of how human-made EMFs at non-thermal levels trigger dysfunction in voltage-gated ion channels (VGICs) in cell membranes. This induces the overproduction of ROS and OS, which are responsible for most known adverse biological and health effects, including DNA damage and related pathologies.
Biochemistry of radical oxygen species:
The electron transport chain (ETC) in the inner mitochondrial membrane is a major source of ROS in all cells and probably accounts for 50–90% of total cellular ROS production under normal conditions. In spermatozoa exposed to WC-EMF, electron leakage from the ETC was found to originate from complex III when tested alongside complex III inhibitors. When considering the mitochondrial causes of OS, Ca²+ plays a key role. While a physiological increase in mitochondrial Ca²+ can stimulate ATP production when energy demand is high, it can also lead to increased ROS formation. Excessive Ca²+ accumulation can lead to mitochondrial dysfunction, decreasing ATP production and more importantly further increasing ROS production and apoptotic factors. Ca²+ can affect mitochondria by regulating important mitochondria-specific dehydrogenases. Therefore, careful control of mitochondrial Ca²+ levels is essential for ROS homeostasis. EMF-induced disruption of Ca²+ channels can lead to ROS overproduction.
NADPH/NADH oxidases (NOXs) catalyze the production of free superoxide anions by transferring electrons from NAD(P)H to oxygen. NOXs are also activated by cytosolic Ca²+ and have a Ca²+-binding site in addition to their H+ voltage-gated channel. NOXs can account for 10–30% of total ROS production in neurons under basal conditions. However, their contribution can increase significantly during neuronal activation or inflammation. NOXs have been identified as an important target for human-induced EMFs.
Nitric oxide synthases (NOS) are specific enzymes found in all animal and plant cells that produce nitric oxide free radicals (NO•). An increase in Ca²+ and NO- concentrations in cells has been found to be triggered very rapidly (within a few seconds) by EMF exposure. The induction of DNA damage by peroxynitrite is blocked by NOS inhibitors and antioxidants.
Furthermore, disruption of voltage-gated Na+ , K+ , Mg²+ and Ca²+ ion channels (VGICs) impairs the function of Na+/K+ pumps (ATPase) and Ca²+ pumps in plasma membranes of all cells. In addition to its role as an ion pump, the Na+/K+-ATPase acts as a signal regulator that transmits signals from the plasma membrane to intracellular organelles. It also normalizes the Na+/K+ balance in cells, for example, after disruption of VGICs. It is well known that ELF EMFs affect the activity of Na+/K+-ATPase and that changes in its activity are related to ROS production in the mitochondria. Martin Pall found a link between EMF-induced dysfunction of voltage-gated calcium channels and NO•/ONOO- overproduction. In the presence of H+, peroxynitrite can easily decompose to OH• and NO2-.
The superoxide anion radical (O2•−), produced by mitochondria or NADH/NADPH oxidase (NOX) is catalyzed by superoxide dismutase (SOD) in the cytosol or mitochondria and converted to hydrogen peroxide (H2O2). H2O2 can reach any location in the cell, including the nucleus, where it can be converted to the highly potent hydroxyl radical (OH•), which can damage any biological molecule, including DNA.
Anthropogenic EMFs and VGICs:
Normally, voltage-gated ion channels (VGICs) switch between open and closed states in response to membrane voltage changes of ≥ 30 mV, which exert forces on their voltage sensors. More specifically, VGICs respond to changes between -30 and -100 mV. VGICs can also respond to very weak polarized, coherent, and slowly fluctuating EMFs down to 10-⁵ V/m via the forced oscillation that such EMFs induce on moving ions in close proximity (< 1 nm) to the sensors (ion forced oscillation: IFO). The IFO-VGIC mechanism postulates that biological activity is proportional to EMF intensity and inversely proportional to frequency. Thus, the effects reported in the literature are caused by low frequency (ULF/ELF/VLF) EMFs, not high frequency (pure radiofrequency/microwave) EMFs. In addition, pulsed EMFs are significantly more bioactive than their continuous (non-pulsed) counterparts. VGICs do not simply respond to the presence of an unchanging (static) electric field; otherwise, they would constantly open and close chaotically, and life could not be sustained. For this reason, the geomagnetic field (GMF) is not particularly bioactive under normal conditions but becomes bioactive when the normal intensity changes by about 20% during magnetic storms. Dysfunction of ion channels affects otherwise carefully controlled intracellular ion concentrations, disturbing the cell's electrochemical balance and homeostasis, including its intracellular redox status, an index of its ROS content. The ROS regulatory system is closely linked to the Ca²+ signaling system. Dysfunction of the Ca²+ channels in the plasma or mitochondrial membrane leads to an interruption of the signaling system and an increase in the ROS concentration in the cell. Therefore, ion channel malfunction leads to ROS overproduction, which further amplifies ion channel malfunction. Clearly, we are dealing here with a vicious cycle in which VGIC dysfunction leads to OS in cells, which disrupts the ion channels further and leads to even more pronounced OS.