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首页> 美国卫生研究院文献>PLoS Clinical Trials >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
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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

机译：暴露于极低频电磁场会通过增加AA / PGE2和EP受体介导的cAMP / PKA途径来调节大鼠小脑颗粒细胞中的Na +电流

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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.
机译：尽管以前已经研究了极低频电磁场（ELF-EMF）对Ca 2 + 通道活性的调制，但很少有报道涉及此类磁场对电压激活Na的活性的影响。 + 频道（导航）。在这里，我们研究了ELF-EMF对大鼠小脑颗粒细胞（GCs）Nav活性的影响。我们的研究结果表明，将小脑GC暴露于ELF-EMF 10-60分钟可显着增加Nav电流（I Na），时间依赖性和强度依赖性可提高30-125％。通过ELF-EMF刺激，Nav通道稳态激活曲线（而不是稳态灭活曲线）向超极化显着移动（5.2 mV）。这种现象类似于小脑GC中花生四烯酸（AA）和前列腺素E2（PGE2）胞内应用对I Na的影响。在暴露于ELF-EMF之后，观察到小脑GC中细胞内AA，PGE2和磷酸化PKA的水平增加。 Western印迹表明，小脑GC膜上的NaV 1.2蛋白增加，暴露于ELF-EMF后，NaV 1.2蛋白的总表达水平不受影响。环氧合酶抑制剂和PGE2受体（EP）拮抗剂能够消除ELF-EMF诱导的磷酸化PKA和I Na的增加。此外，ELF-EMF暴露可显着增强小脑GC中PLA2的活性，但不影响COX-1或COX-2的活性。总之，这些数据首次证明，通过cPLA2 AA PGE2 EP受体PKA信号传导途径的ELF-EMF暴露可明显增加神经元I Na。

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