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Melatonin protects rat cerebellar granule cells against electromagnetic field-induced increases in Na+ currents through intracellular Ca2+ release
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2014
- Publisher :
- John Wiley & Sons, Ltd, 2014.
-
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.
- Subjects :
- Male
medicine.medical_specialty
Cerebellum
Na+ currents
animal structures
Patch-Clamp Techniques
Calmodulin
medicine.drug_class
Stimulation
melatonin
Voltage-Gated Sodium Channels
Cytoplasmic Granules
Protective Agents
Calcium in biology
Antioxidants
Rats, Sprague-Dawley
Ca2+ release
Mice
Calcium imaging
Electromagnetic Fields
Internal medicine
medicine
Animals
Patch clamp
Phosphorylation
Cells, Cultured
biology
Chemistry
ELF-EMF
Cell Biology
Original Articles
respiratory system
Receptor antagonist
Cell biology
Rats
medicine.anatomical_structure
Endocrinology
cerebellar granule cells
biology.protein
Molecular Medicine
Calcium
Oxidation-Reduction
Intracellular
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15824934 and 15821838
- Volume :
- 18
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....83508c6f181414b088b9bc02384ad053