Exposure to 50 Hz magnetic field modulates GABAA currents in cerebellar granule neurons through an EP receptor-mediated PKC pathway.
Exposure to 50 Hz magnetic field modulates GABAA currents in cerebellar granule neurons through an EP receptor-mediated PKC pathway.
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DOI：
10.1111/jcmm.12626
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发表时间：
2015-10
影响因子：
5.3
通讯作者：
Mei YA
中科院分区：
文献类型：
--
作者：
Yang G;Ren Z;Mei YA
我们实验室和其他实验室的先前工作表明，暴露于50 Hz磁场（ELF-MF）能够改变离子通道功能。然而，很少有研究探讨MF对γ-氨基丁酸（GABA）A型受体（GABAARs）通道功能的影响，这是神经元整体兴奋性的基础。在这里，我们的主要目标是揭示ELF-MF对大鼠小脑颗粒神经元（CGNs）GABAARs活性的潜在影响。我们的结果表明，将CGN暴露于ImT ELF-MF 60分钟。显着增加GABAAR电流，而不改变对GABA的敏感性。然而，激活PKA的db-cAMP未能做到这一点，但导致略有下降，而不是。另一方面，PKC激活或抑制PMA或双和二十二碳六烯酸（DHA）模拟或消除场诱导的GABAAR电流的增加。Westernblot分析显示，细胞内磷酸化PKC（pPKC）水平在60 min后显著升高。ELF-MF暴露，随后通过应用DHA或EP 1受体特异性（前列腺素E受体1）拮抗剂（SC 19220）而不是EP 2-EP 4受体特异性拮抗剂来阻断。SC 19220还显著抑制ELF-MF诱导的GABAAR电流升高。总之，这些数据首次明显证明了神经元GABAA电流通过ELF-MF暴露显著增加，并且还表明这些作用通过EP 1受体介导的PKC途径介导。未来的工作将集中在更全面的分析这些影响的生理和/或病理后果。
Previous work from both our lab and others have indicated that exposure to 50 Hz magnetic fields (ELF-MF) was able to modify ion channel functions. However, very few studies have investigated the effects of MF on γ-aminobutyric acid (GABA) type A receptors (GABAARs) channel functioning, which are fundamental to overall neuronal excitability. Here, our major goal is to reveal the potential effects of ELF-MF on GABAARs activity in rat cerebellar granule neurons (CGNs). Our results indicated that exposing CGNs to 1 mT ELF-MF for 60 min. significantly increased GABAAR currents without modifying sensitivity to GABA. However, activation of PKA by db-cAMP failed to do so, but led to a slight decrease instead. On the other hand, PKC activation or inhibition by PMA or Bis and Docosahexaenoic acid (DHA) mimicked or eliminated the field-induced-increase of GABAAR currents. Western blot analysis indicated that the intracellular levels of phosphorylated PKC (pPKC) were significantly elevated after 60 min. of ELF-MF exposure, which was subsequently blocked by application of DHA or EP1 receptor-specific (prostaglandin E receptor 1) antagonist (SC19220), but not by EP2-EP4 receptor-specific antagonists. SC19220 also significantly inhibited the ELF-MF-induced elevation on GABAAR currents. Together, these data obviously demonstrated for the first time that neuronal GABAA currents are significantly increased by ELF-MF exposure, and also suggest that these effects are mediated via an EP1 receptor-mediated PKC pathway. Future work will focus on a more comprehensive analysis of the physiological and/or pathological consequences of these effects.