New Study on EMF Mechanisms of Action: “Plausible Mechanisms of Action for Low-Intensity EMR Exposure”

Pall, Martin (2013). Journal of Cellular and Molecular Medicine

Pall, M. L. (2013), Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. Journal of Cellular and Molecular Medicine. doi: 10.1111/jcmm.12088

The mechanisms by which extremely low and microwave frequency EMFs produce non-thermal effects in humans and animals has been a great puzzle for scientists, because these fields are comprised of low-energy photons with energies thought too low to affect our physiology.


  • A plausible mechanism is highlighted in this new study. This paper by Martin Pall disproves the popular claims that these biological effects cannot exist for lack of a plausible mechanism of action. A careful review of twenty-three studies shows that calcium channels may be the key mechanism for understanding the biological effects of EMFs.
  • These studies shine light on our physiological responses to a variety of EMFs, including extremely low frequency EMFs (such as alternating currents in wiring), a variety of microwave and radiofrequency fields, nanosecond EMF pulses, and static electric and magnetic fields.
  • The role of calcium: Electromagnetic fields target voltage-gated calcium channels (VGCCs) by partially depolarizing the electrical charge across a cell’s plasma membrane, which causes VGCCs to increase production of intracellular calcium. The role of increased intracellular calcium following EMF exposure has been well documented for more than 20 years. Drugs that block the action of VGCCs greatly reduce these effects (for example, “calcium channel blockers” such as verapamil).
  • The Role of Nitric Oxide: Intracellular calcium then stimulates the synthesis of nitric oxide (NO) via two different pathways: the G-kinase pathway and the peroxynitrite pathway. Nitric oxide can have beneficial or adverse effects, depending on which of the two pathways it follows.
  • G-kinase pathway: This pathway utilizes the production of cGMP and G-kinase and produces beneficial physiologic effects, such as EMF stimulation of bone growth by increased osteoblast activity, which is a promising therapeutic application of EMFs.
  • Peroxynitrite pathway: This pathway produces most of the known adverse physiological effects. Nitric oxide is a precursor of peroxynitrite, a potent source of free radicals (including the hydroxyl radical and NO2 radical) that cause significant oxidative stress. Peroxynitrite induces single-strand breaks in the DNA. EMF-related oxidative stress and DNA damage can be mediated by certain antioxidants and nitric oxide synthase inhibitors.
  • Future Research: Knowing these mechanisms by which EMFs affect human tissues will help make future studies more focused and productive, as researchers will at least “know where to look.” Future EMF studies should explore the roles of VGCCs, intracellular calcium, nitric oxide, and possibly cGMP and peroxynitrite.
  • Electrical and Chemical Sensitivity: This information lays the groundwork for future studies about electromagnetic hypersensitivity (EHS) and multiple chemical sensitivity (MCS), which may involve the mechanisms described above. In MCS, chemicals act by indirectly activating NMDA receptors (glutamate receptors), which have many properties similar to VGCCs.



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.


Read Full Study:

Pall, M. L. (2013), Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. Journal of Cellular and Molecular Medicine. doi: 10.1111/jcmm.12088


For More Information on Known EMF Mechanisms of Action see the ICEMS Monograph: “Non-Thermal Effects and Mechanisms of Interaction Between Electromagnetic Fields and Living Matter”   (2010)

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