Exposure to Extremely Low-Frequency Electromagnetic Fields Modulates Na+ Currents in Rat Cerebellar Granule Cells through Increase of AA/PGE2 and EP Receptor-Mediated cAMP/PKA Pathway

Although the modulation of Ca 2+ channel activity by extremely low-frequency electromagnetic fields (ELF-EMF) has been studied previously, few reports have addressed the effects of such fields on the activity of voltage-activated Na + channels (Na v ). Here, we investigated the effects of ELF-EMF on Na v activity in rat cerebellar granule cells (GCs). Our results reveal that exposing cerebellar GCs to ELF-EMF for 10–60 min significantly increased Na v currents ( I Na ) by 30–125% in a time- and intensity-dependent manner. The Na v channel steady-state activation curve, but not the steady-state inactivation curve, was significantly shifted (by 5.2 mV) towards hyperpolarization by ELF-EMF stimulation. This phenomenon is similar to the effect of intracellular application of arachidonic acid (AA) and prostaglandin E 2 (PGE 2 ) on I Na in cerebellar GCs. Increases in intracellular AA, PGE 2 and phosphorylated PKA levels in cerebellar GCs were observed following ELF-EMF exposure. Western blottings indicated that the Na V 1.2 protein on the cerebellar GCs membrane was increased, the total expression levels of Na V 1.2 protein were not affected after exposure to ELF-EMF. Cyclooxygenase inhibitors and PGE 2 receptor (EP) antagonists were able to eliminate this ELF-EMF-induced increase in phosphorylated PKA and I Na . In addition, ELF-EMF exposure significantly enhanced the activity of PLA 2 in cerebellar GCs but did not affect COX-1 or COX-2 activity. Together, these data demonstrate for the first time that neuronal I Na is significantly increased by ELF-EMF exposure via a cPLA2 AA PGE 2 EP receptors PKA signaling pathway.