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.
Highlights
A number of studies have noted that exposure to extremely lowfrequency electromagnetic fields (ELF-EMF) alter animal behaviors and modulate biological effects, including changes in gene expression, regulation of cell survival and promotion of cell differentiation [1,2,3]
When cerebellar granule cells (GCs) were exposed to ELF-EMF for 30 min, 60 min or 90 min, the density of the increased Nav currents (INa) increased by 67.1% 64.38% (n = 8, P,0.05), 125.6% 68.26% (n = 16, P,0.05), 102.4% 64.1% (n = 9, P,0.05), respectively, compared to controls (Fig. 1B)
Because a previous study indicated that when cells are exposed to ELF-EMF over a long term, their levels of protein expression may be affected [5], which will be difficult to further identify the primary factor involved in the ELF-EMFinduced INa increase
Summary
A number of studies have noted that exposure to extremely lowfrequency electromagnetic fields (ELF-EMF) alter animal behaviors and modulate biological effects, including changes in gene expression, regulation of cell survival and promotion of cell differentiation [1,2,3]. Very few studies have investigated the effects of EMF on sodium channels, in particular, the voltage-gated sodium (Nav) channels which are highly expressed in neurons. Recent studies have revealed that NaV channels participate in the rising phase of the neuronal action potential and contribute to many cellular functions including apoptosis, motility and secretory membrane activity [11,12,13]. The EMF exposure was recently reported to modulate neuronal excitation and neurogenesis, which may be related to NaV channel activity [8,14,15]. A thorough investigation of the influence of ELF-EMF on NaV channels and the corresponding mechanism of action could help to uncover the effects of ELF-EMF-induced biological effects on brain physiology, pathogenesis and neural development
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