Study type: Medical/biological study (experimental study)

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

Published in: J Cell Mol Med 2014; 18 (6): 1060-1070

Aim of study (acc. to author)

To investigate the effects of melatonin on extremely low frequency magnetic field-induced activation of voltage-gated sodium channels and the related pathways in rat cerebellar granule cells.

Background/further details

In a previous study (He et al. 2013), the authors showed that extremely low frequency magnetic fields significantly activated the voltage-gated sodium channels of cerebellar granule cells. Melatonin is known to modulate the delay in outward rectifying K+ channels, resulting amongst others in a protection against apoptosis. However, only few studies examined the effect of melatonin on Na+ channels, especially in combination with extremely low frequency magnetic fields.
Cell cultures were examined in 5 groups: 1.) sham exposure, 2.) magnetic field exposure, 3.) magnetic field exposure + 1 µM melatonin, 4.) magnetic field exposure + 5 µM melatonin and 5.) sham exposure + 5 µM melatonin. To verify the results, a melatonin receptor agonist (IIK-7) or an antagonist (4-P-PDOT) were partially added as well as an calmodulin inhibitor (KN93) and a ryanodine-sensitive receptor blocker (inhibits the release of Ca2+).

Endpoint

Exposure

Exposure Parameters
Exposure 1: 50 Hz
Exposure duration: continuous for 60 minutes

Exposure 1

Main characteristics
Frequency 50 Hz
Type
Waveform
Exposure duration continuous for 60 minutes
Exposure setup
Exposure source
Setup magnetic field was generated by a pair of Helmholtz coils placed in opposition to each other, coils were powered by a generator system that produced sinusoidal input voltage, device was powered by an AC power generator, magnetic field frequency and density were monitored by a sensor that was connected to a digital multimeter, geometry of the system assured a uniform field for the exposed cultured cells, surfaces of the culture plates were parallel to the force lines of the alternating magnetic field in the solenoid, maximum temperature increase recorded in the exposed cultures was 0.4 ± 0.1°C
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 1 mT - measured - -

Reference articles

  • Varani K et al. (2012): Effect of pulsed electromagnetic field exposure on adenosine receptors in rat brain.
  • Ongaro A et al. (2012): Electromagnetic fields (EMFs) and adenosine receptors modulate prostaglandin E(2) and cytokine release in human osteoarthritic synovial fibroblasts.

Exposed system:

Methods Endpoint/measurement parameters/methodology

Investigated system:
Time of investigation:
  • after exposure

Main outcome of study (acc. to author)

In magnetic field exposed cells, the sodium current in voltage-gated sodium channels was significantly increased compared to the control group. An addition of 5 µM melatonin inhibited the exposure-induced effect. This inhibitory effect of melatonin was mimicked by a melatonin receptor agonist and was diminished by an antagonist. The voltage-gated sodium channel steady-state activation curve was significantly shifted towards hyperpolarization by the magnetic field exposure, but this effect was diminished by an addition of melatonin.
The protein expression level of phosphorylated protein kinase A was significantly elevated in exposed cell cultures (also with the addition of melatonin or a melatonin receptor agonist) in comparison to the unexposed control group.
The intracellular Ca2+ level was significantly increased by melatonin and by melatonin in addition with magnetic field exposure compared to the control group, but not by magnetic field exposure alone and not in the presence of a ryanodine-sensitive receptor blocker. The inhibitory effect of melatonin on the magnetic field exposure-induced activation of voltage-gated sodium channels was diminished by a calmodulin inhibitor.
The authors conclude that melatonin could protect against the magnetic field-induced activation of voltage-gated sodium channels in cerebellar granule cells of rats through an elevated Ca2+ release.

Study character:

Study funded by

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