Melatonin protects rat cerebellar granule cells against electromagnetic field‐induced increases in Na⁺ currents through intracellular Ca²⁺ 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 Ca2+ level, but it significantly elevated the intracellular Ca2+ 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 Ca2+ influx-induced Ca2+ release.

<p>Melatonin MT2 receptor agonist IIK-7 produces antinociception by modulation of ROS and suppression of spinal microglial activation in neuropathic pain rats</p>

“…This agonist is known to have 90-folds more selectivity toward MT2 receptor (pKi =10.30) subtype over MT1 (pKi =8.34) with a 6-fold higher affinity toward MT2 receptor subtype than MLT 16. IIK-7 is known to promote sleep and protect the cells from electromagnetic stress like MLT 17,18. However, to date, there are no reports on the anti-nociceptive properties of this agonist.…”

GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat cerebellar granule neurons

“…Whether GDF-15 modulates [Ca 2+ ] i in CGNs and the mechanisms that are involved is unknown. In the present study, we evaluated the effect of GDF-15 on [Ca 2+ ] i using Ca 2+ imaging while simultaneously recording inward Ca 2+ current ( I Ca ), since changes in [Ca 2+ ] i in CGNs are associated with Ca 2+ influx-dependent Ca 2+ release [ 20 , 21 ]. We also examined whether the same signalling pathways and receptors identified in our previous study are activated by GDF-15 under these conditions.…”

Effect of electromagnetic fields and antioxidants on the trace element content of rat teeth

“…A previous study examined the impact of magnetic field exposure on oxidative stress created by EMFs and identified protective impacts 27. In our study, we found that treatment with an antioxidant (MLT or GL) caused the TE concentrations (that were changed by high-voltage ELF-EMFs) to return to their normal values.…”