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.
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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DOI：
10.1371/journal.pone.0054376
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mei YA
中科院分区：
文献类型：
--
作者：
He YL;Liu DD;Fang YJ;Zhan XQ;Yao JJ;Mei YA
虽然以前已经研究过极低频电磁场（ELF-EMF）对Ca2+通道活性的调制，但很少有报道涉及这些场对电压激活的Na+通道（Nav）活性的影响。本文研究了ELF-EMF对大鼠小脑颗粒细胞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，以时间和强度依赖的方式显着增加了30-125%的Nav电流（I Na）。在ELF-EMF刺激下，Nav通道稳态激活曲线向超极化方向显著偏移（偏移幅度为5.2 mV），而稳态失活曲线未发生明显偏移。这种现象类似于细胞内应用花生四烯酸（AA）和前列腺素E2 （PGE2）对小脑GCs中Na的影响。ELF-EMF暴露后，观察到小脑GCs细胞内AA、PGE2和磷酸化PKA水平升高。Western blot结果显示，ELF-EMF暴露后，小脑GCs膜上NaV 1.2蛋白表达量增加，但NaV 1.2蛋白总表达量未受影响。环加氧酶抑制剂和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暴露显著增强了小脑GCs中PLA2的活性，但不影响COX-1或COX-2的活性。综上所述，这些数据首次证明了ELF-EMF暴露通过cPLA2 AA PGE2 EP受体PKA信号通路显著增加神经元I Na。
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.