title: Exposure to 50 Hz magnetic field modulates GABAA currents in cerebellar granule neurons through an EP receptor-mediated PKC pathway.
abstract: 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 (GABA(A) Rs) channel functioning, which are fundamental to overall neuronal excitability. Here, our major goal is to reveal the potential effects of ELF-MF on GABA(A) Rs activity in rat cerebellar granule neurons (CGNs). Our results indicated that exposing CGNs to 1 mT ELF-MF for 60 min. significantly increased GABA(A) R 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 GABA(A) R 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 GABA(A) R currents. Together, these data obviously demonstrated for the first time that neuronal GABA(A) 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.
authors.affiliation: School of Life Sciences, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ren
authors.affiliation: School of Life Sciences, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Yan-Ai
authors.initials: YA
authors.lastname: Mei
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D060526:Magnetic Fields; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012044:Regression Analysis; D015398:Signal Transduction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D011963:Receptors, GABA-A; D058306:Receptors, Prostaglandin E, EP1 Subtype; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C
keywords: 50 Hz magnetic fields; EP receptors; GABAA currents; PKC pathway; rat cerebellar granule neurons