title: Exposure to extremely low-frequency electromagnetic fields inhibits T-type calcium channels via AA/LTE4 signaling pathway.
abstract: Extremely low-frequency electromagnetic fields (ELF-EMF) causes various biological effects through altering intracellular calcium homeostasis. The role of high voltage-gated (HVA) calcium channels in ELF-EMF induced effects has been extensively studied. However, the effect of ELF-EMF on low-voltage-gated (LVA) T-type calcium channels has not been reported. In this study, we test the effect of ELF-EMF (50Hz) on human T-type calcium channels transfected in HEK293 cells. Conversely to its stimulant effects on HVA channels, ELF-EMF exposure inhibited all T-type (Cav3.1, Cav3.2 and Cav3.3) channels. Neither the protein expression nor the steady-state activation and inactivation kinetics of Cav3.2 channels were altered by ELF-EMF (50Hz, 0.2mT) exposure. Exposure to ELF-EMF increased both arachidonic acid (AA) and leukotriene E4 (LTE4) levels in HEK293 cells. CAY10502 and bestatin, which block the increase of AA and LTE4 respectively, abrogated the ELF-EMF inhibitory effect on Cav3.2 channels. Exogenous LTE4 mimicked the ELF-EMF inhibition of T-type calcium channels. ELF-EMF (50Hz) inhibits native T-type calcium channels in primary cultured mouse cortical neurons via LTE4. We conclude that 50Hz ELF-EMF inhibits T-type calcium channels through AA/LTE4 signaling pathway.
authors.affiliation: School of Life Sciences, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cui
authors.affiliation: School of Life Sciences, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China.
authors.forename: Yan-Ai
authors.initials: YA
authors.lastname: Mei
authors.affiliation: School of Life Sciences, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200433, China. Electronic address: clhu@fudan.edu.cn.
authors.forename: Changlong
authors.initials: C
authors.lastname: Hu
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004574:Electromagnetic Fields; D057809:HEK293 Cells; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D017999:Leukotriene E4 / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020747:Calcium Channels, T-Type; D016718:Arachidonic Acid; D017999:Leukotriene E4; D002118:Calcium
keywords: Extremely low-frequency electromagnetic fields; T-type calcium channels; The cysteinyl leukotrienes