title: Melatonin protects rat cerebellar granule cells against electromagnetic field-induced increases in Na(+) currents through intracellular Ca(2+) release.
abstract: Although melatonin (MT) has been reported to protect cells against oxidative damage induced by electromagnetic radiation, few reports have addressed whether there are other protective mechanisms. Here, we investigated the effects of MT on extremely low-frequency electromagnetic field (ELF-EMF)-induced Nav activity in rat cerebellar granule cells (GCs). Exposing cerebellar GCs to ELF-EMF for 60 min. significantly increased the Nav current (INa ) densities by 62.5%. MT (5 μM) inhibited the ELF-EMF-induced INa increase. This inhibitory effect of MT is mimicked by an MT2 receptor agonist and was eliminated by an MT2 receptor antagonist. The Nav channel steady-state activation curve was significantly shifted towards hyperpolarization by ELF-EMF stimulation but remained unchanged by MT in cerebellar GC that were either exposed or not exposed to ELF-EMF. ELF-EMF exposure significantly increased the intracellular levels of phosphorylated PKA in cerebellar GCs, and both MT and IIK-7 did not reduce the ELF-EMF-induced increase in phosphorylated PKA. The inhibitory effects of MT on ELF-EMF-induced Nav activity was greatly reduced by the calmodulin inhibitor KN93. Calcium imaging showed that MT did not increase the basal intracellular Ca(2+) level, but it significantly elevated the intracellular Ca(2+) level evoked by the high K(+) stimulation in cerebellar GC that were either exposed or not exposed to ELF-EMF. In the presence of ruthenium red, a ryanodine-sensitive receptor blocker, the MT-induced increase in intracellular calcium levels was reduced. Our data show for the first time that MT protects against neuronal INa that result from ELF-EMF exposure through Ca(2+) influx-induced Ca(2+) release.
authors.affiliation: School of Life Sciences, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ren
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Qian-Ru
authors.initials: QR
authors.lastname: Zhao
authors.forename: Yan-Ai
authors.initials: YA
authors.lastname: Mei
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D004574:Electromagnetic Fields / Q000009:adverse effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D061566:Voltage-Gated Sodium Channels; D008550:Melatonin; D002118:Calcium
keywords: Ca2+ release; ELF-EMF; Na+ currents; cerebellar granule cells; melatonin