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

Abstract

Although the modulation of Ca2+ 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 (Nav). Here, we investigated the effects of ELF-EMF on Nav activity in rat cerebellar granule cells (GCs). Our results reveal that exposing cerebellar GCs to ELF-EMF for 10–60 min significantly increased Nav currents (I Na) by 30–125% in a time- and intensity-dependent manner. The Nav 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 E2 (PGE2) on I Na in cerebellar GCs. Increases in intracellular AA, PGE2 and phosphorylated PKA levels in cerebellar GCs were observed following ELF-EMF exposure. Western blottings indicated that the NaV 1.2 protein on the cerebellar GCs membrane was increased, the total expression levels of NaV 1.2 protein were not affected after exposure to ELF-EMF. Cyclooxygenase inhibitors and PGE2 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 PLA2 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 PGE2 EP receptors PKA signaling pathway.

Melatonin protects rat cerebellar granule cells against electromagnetic field‐induced increases in Na+ currents through intracellular Ca2+ release

“…in this study. Similar to our previous report , when cerebellar GCs were exposed to 1 mT ELF‐EMF for 60 min., the amplitude of the I Na increased by ~62.5 ± 6.6% ( n = 25, P < 0.05) compared with cells that were not exposed to ELF‐EMF ( n = 33, Fig. A).…”

“…An I Na was elicited by a depolarization step to −20 mV from the holding potential of −100 mV. Our previous study demonstrated that the increase in I Na amplitude induced by ELF‐EMF exposure was time dependent, and when cerebellar GCs were exposed to 1 mT ELF‐EMF for 60 min., the amplitude of the I Na increased significantly and was stable . Moreover, exposure cell or neuron to 1–5 mT EMF with short time was reported by Bai and Moghadam's studies .…”

“…Our previous data indicated that ELF‐EMF exposure significantly shifted the voltage dependence of the steady‐state activation curve of I Na , but the steady‐state inactivation curve of I Na did not significantly shift upon exposure to ELF‐EMF . We further investigated whether the inhibitory effects of MT on ELF‐EMF‐induced I Na activity were because of modulation of the voltage‐gating properties of I Na channels.…”

Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

“…This effect was detected also in adherent cells, as exposure at 50 Hz and 0.4 mT for 5 min induced clustering of epidermal growth factor receptors and activation of Ras GTPases in Chinese hamster lung (CHL) fibroblasts [21]. Other signaling pathways that are activated by short-term ELF-MF include cyclic AMP/protein kinase A (cAMP/PKA) in human skin fibroblasts exposed to 20 Hz and 7 -8 mT radiation for 60 min [22], as well as in rat cerebellar granule cells exposed to 60 Hz and 1 mT for 10 -90 min [23]. Another important signaling mechanism that appears to be influenced by ELF-MF is the elevation of intracellular Ca 2+ in exposed cells [24,25] within 1 min of exposure to ELF-MF at 50 Hz and 0.1 mT.…”

PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway

“…In the present of SC19220, PGE 2 only increased pPKC levels by 12.0 ± 7.8% ( n = 5, p >0.05 compared with control). To further verify that only EP1 was responsible for the intracellular effects of PGE 2 , we administered either an EP2 or EP4 receptor antagonist, AH6809 or AH23848, at concentrations that we have previously demonstrated to be effective [25,32]. Either antagonist was unable to eliminate the effects of PGE 2 on pPKC levels (Fig.…”