Melatonin protects rat cerebellar granule cells against electromagnetic field-induced increases in Na(+) currents through intracellular Ca(2+) release

J Cell Mol Med · 2014 · Mixed · Low evidence

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MixedLow evidencePaper 2745

Study snapshot

PublicationJ Cell Mol Med · 2014

Study typein_vitro

Reported directionMixed

Evidence ratingLow

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.

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionmixed

PopulationRat cerebellar granule cells (GCs)

Sample sizeNot supplied

ExposureELF · 60 min

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Exposing rat cerebellar granule cells to ELF-EMF for 60 min increased Nav current densities by 62.5% and shifted the Nav steady-state activation curve toward hyperpolarization. Melatonin (5 μM) inhibited the ELF-EMF-induced increase in Nav current; this effect was linked to MT2 receptor signaling and was reduced by a calmodulin inhibitor, with data suggesting involvement of Ca(2+) influx-induced Ca(2+) release (ryanodine-sensitive).

Outcomes measured

Nav current (INa) density
Nav channel steady-state activation curve shift
Intracellular phosphorylated PKA levels
Intracellular Ca(2+) levels (basal and high K+-evoked)

Limitations

No exposure frequency or field strength reported in the abstract
In vitro cell model; relevance to in vivo outcomes not established in the abstract
Sample size and replication details not provided in the abstract

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": "ELF",
    "source": "electromagnetic field (ELF-EMF) exposure",
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": "60 min"
  },
  "population": "Rat cerebellar granule cells (GCs)",
  "sample_size": null,
  "outcomes": [
    "Nav current (INa) density",
    "Nav channel steady-state activation curve shift",
    "Intracellular phosphorylated PKA levels",
    "Intracellular Ca(2+) levels (basal and high K+-evoked)"
  ],
  "main_findings": "Exposing rat cerebellar granule cells to ELF-EMF for 60 min increased Nav current densities by 62.5% and shifted the Nav steady-state activation curve toward hyperpolarization. Melatonin (5 μM) inhibited the ELF-EMF-induced increase in Nav current; this effect was linked to MT2 receptor signaling and was reduced by a calmodulin inhibitor, with data suggesting involvement of Ca(2+) influx-induced Ca(2+) release (ryanodine-sensitive).",
  "effect_direction": "mixed",
  "limitations": [
    "No exposure frequency or field strength reported in the abstract",
    "In vitro cell model; relevance to in vivo outcomes not established in the abstract",
    "Sample size and replication details not provided in the abstract"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "melatonin",
    "ELF-EMF",
    "Nav current",
    "cerebellar granule cells",
    "MT2 receptor",
    "calmodulin",
    "PKA phosphorylation",
    "intracellular calcium",
    "ryanodine receptor",
    "ruthenium red"
  ],
  "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1111/jcmm.12250
PubMed: 24548607

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