Electromagnetic fields instantaneously modulate nitric oxide signaling in challenged biological systems

• Published in: Biochemical and biophysical research communications Vol. 426; no. 3; pp. 330 - 333
• Main Author: Pilla, Arthur A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.09.2012
• Subjects: Anti-inflammatory; Calcium - metabolism; Calmodulin; Calmodulin - antagonists & inhibitors; Cell Line; Cell Line, Tumor; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Electromagnetic Fields; EMF; Fibroblasts - drug effects; Fibroblasts - metabolism; First messenger; Humans; Lipopolysaccharides - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Signal Transduction; Signaling; Sulfonamides - pharmacology; First messenger; Signaling; Anti-inflammatory; Nitric oxide; Calmodulin; EMF
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.08.078

► Effect of EMF on NO release from neuronal cultures was measured in real-time. ► Cells were acutely challenged with LPS which causes increase in cytosolic Ca2+. ► EMF increased NO 3-fold in <5s as measured with NO selective electrode. ► EMF effect blocked with W-7 in fibroblast cultures after 15min exposure. ► Results support effect on NO signaling as principal mechanism of EMF bioeffects. This study shows that a non-thermal pulse-modulated RF signal (PRF), configured to modulate calmodulin (CaM) activation via acceleration of Ca2+ 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.