Exposure to extremely low-frequency electromagnetic fields modulates Na+ currents in rat cerebellar granule cells through increase of AA/PGE2 and EP receptor-mediated cAMP/PKA pathway.

PloS one · 2013 · Mixed · Low evidence

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MixedLow evidencePaper 4627

Study snapshot

PublicationPloS one · 2013

Study typein_vitro

Reported directionMixed

Evidence ratingLow

Abstract

Although the modulation of Ca(2+) channel activity by extremely low-frequency electromagnetic fields (ELF-EMF) has been studied previously, few reports have addressed the effects of such fields on the activity of voltage-activated Na(+) channels (Na(v)). Here, we investigated the effects of ELF-EMF on Na(v) activity in rat cerebellar granule cells (GCs). Our results reveal that exposing cerebellar GCs to ELF-EMF for 10-60 min significantly increased Na(v) currents (I(Na)) by 30-125% in a time- and intensity-dependent manner. The Na(v) channel steady-state activation curve, but not the steady-state inactivation curve, was significantly shifted (by 5.2 mV) towards hyperpolarization by ELF-EMF stimulation. This phenomenon is similar to the effect of intracellular application of arachidonic acid (AA) and prostaglandin E(2) (PGE(2)) on I(Na) in cerebellar GCs. Increases in intracellular AA, PGE(2) and phosphorylated PKA levels in cerebellar GCs were observed following ELF-EMF exposure. Western blottings indicated that the Na(V) 1.2 protein on the cerebellar GCs membrane was increased, the total expression levels of Na(V) 1.2 protein were not affected after exposure to ELF-EMF. Cyclooxygenase inhibitors and PGE(2) receptor (EP) antagonists were able to eliminate this ELF-EMF-induced increase in phosphorylated PKA and I(Na). In addition, ELF-EMF exposure significantly enhanced the activity of PLA(2) in cerebellar GCs but did not affect COX-1 or COX-2 activity. Together, these data demonstrate for the first time that neuronal I(Na) is significantly increased by ELF-EMF exposure via a cPLA2 AA PGE(2) EP receptors PKA signaling pathway.

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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 · 10–60 min

Evidence strengthLowConfidence: 78% · Peer reviewed: yes

Main findings

Exposing rat cerebellar granule cells to ELF-EMF for 10–60 min increased Na(v) currents by 30–125% in a time- and intensity-dependent manner and shifted the Na(v) steady-state activation curve ~5.2 mV toward hyperpolarization without changing steady-state inactivation. ELF-EMF exposure increased intracellular AA, PGE2, phosphorylated PKA, membrane Na(V)1.2 (without changing total Na(V)1.2), and PLA2 activity; cyclooxygenase inhibitors and EP receptor antagonists eliminated the ELF-EMF-induced increases in phosphorylated PKA and I(Na), while COX-1/COX-2 activity was not affected.

Outcomes measured

Voltage-activated Na+ channel currents (I(Na))
Na(v) steady-state activation and inactivation curves
Intracellular arachidonic acid (AA) levels
Intracellular prostaglandin E2 (PGE2) levels
Phosphorylated PKA levels
Na(V)1.2 protein on membrane and total expression
Effects of cyclooxygenase inhibitors and EP receptor antagonists on I(Na) and phosphorylated PKA
PLA2 activity
COX-1 and COX-2 activity

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": "ELF",
    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": "10–60 min"
  },
  "population": "Rat cerebellar granule cells (GCs)",
  "sample_size": null,
  "outcomes": [
    "Voltage-activated Na+ channel currents (I(Na))",
    "Na(v) steady-state activation and inactivation curves",
    "Intracellular arachidonic acid (AA) levels",
    "Intracellular prostaglandin E2 (PGE2) levels",
    "Phosphorylated PKA levels",
    "Na(V)1.2 protein on membrane and total expression",
    "Effects of cyclooxygenase inhibitors and EP receptor antagonists on I(Na) and phosphorylated PKA",
    "PLA2 activity",
    "COX-1 and COX-2 activity"
  ],
  "main_findings": "Exposing rat cerebellar granule cells to ELF-EMF for 10–60 min increased Na(v) currents by 30–125% in a time- and intensity-dependent manner and shifted the Na(v) steady-state activation curve ~5.2 mV toward hyperpolarization without changing steady-state inactivation. ELF-EMF exposure increased intracellular AA, PGE2, phosphorylated PKA, membrane Na(V)1.2 (without changing total Na(V)1.2), and PLA2 activity; cyclooxygenase inhibitors and EP receptor antagonists eliminated the ELF-EMF-induced increases in phosphorylated PKA and I(Na), while COX-1/COX-2 activity was not affected.",
  "effect_direction": "mixed",
  "limitations": [],
  "evidence_strength": "low",
  "confidence": 0.78,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "extremely low-frequency electromagnetic fields",
    "ELF-EMF",
    "rat",
    "cerebellar granule cells",
    "Na+ currents",
    "Na(v) channels",
    "Na(V)1.2",
    "arachidonic acid",
    "prostaglandin E2",
    "EP receptor",
    "cAMP/PKA",
    "PLA2",
    "cyclooxygenase inhibitors"
  ],
  "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: 10.1371/journal.pone.0054376
PubMed: 23349866

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