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 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
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.
