研究のタイプ: 医学/生物学の研究 (experimental study)

[超低周波電磁界へのばく露はAA/PGE2経路およびEP受容体介在性cAMP/PKA経路の生成レベル上昇によりラット小脳顆粒細胞のナトリウムイオン電流を変化させる] med./bio.

Exposure to Extremely Low-Frequency Electromagnetic Fields Modulates Na(+) Currents in Rat Cerebellar Granule Cells through Increase of AA/PGE(2) and EP Receptor-Mediated cAMP/PKA Pathway

掲載誌: PLoS One 2013; 8 (1): e54376

この研究では、50Hz、1mTのELF磁界ラット小脳顆粒細胞における電位依存性ナトリウムイオンNa+)チャネル(Nav)の活性に及ぼす影響を調べた細胞実験である。その結果、ELF磁界に10-60分間ばく露した小脳顆粒細胞では、時間及び強度に依存してNav電流が30-125%有意に上昇することが示された;ELF磁界刺激はNavチャネルの定常状態の活性化曲線を過分極の方向に有意にシフトさせたが、定常状態の不活性化曲線はシフトさせなかった;この現象は、小脳顆粒細胞におけるNav電流の上昇に対するアラキドン酸(AA)、プロスタグランジンE2(PGE2)の細胞内投与の影響と類似している;ELF磁界ばく露後に、細胞内のAA、PGE2およびリン酸化PKAレベルの上昇が認められた;ウェスタン・ブロッティングでは、小脳顆粒細胞膜上のNav1.2チャネルのタンパクは増加を示したが、Nav1.2チャネルのタンパクの全発現量はばく露に影響されなかった;シクロオキシゲナーゼ阻害剤およびPGE2受容体拮抗薬は、ELF磁界によって生じたリン酸化PKA及びNav電流の上昇を排除できた;加えて、ELF磁界ばく露小脳顆粒細胞におけるPLA2の活性を有意に高めたが、COX-1またはCOX-2活性には影響しなかった、と報告している。

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研究目的(著者による)

To study the effects of extremely low frequency magnetic fields on voltage-gated sodium ion channels activity in rat cerebellar granule cells (and the related pathway).

詳細情報

Cerebellar granule cells are used as a model for neuronal cell development and apoptosis. The authors have shown previously that the sodium current densities of cerebellar granule cells are modulated by arachidonic acid: elevation of intracellular arachidonic acid levels increases the sodium current of cerebellar granule cells through the prostaglandin E2-mediated activation of the cAMP/protein kinase A pathway. Arachidonic acid can be converted to prostaglandin E2, e.g. by cyclooxygenases. Phospholipase A2 plays an important role in producing intracellular arachidonic acid.

影響評価項目

ばく露

ばく露 パラメータ
ばく露1: 50 Hz
ばく露時間: 10, 30, 60 or 90 min
ばく露2: 50 Hz
ばく露時間: 6 h or 12 h

General information

Maximum temperature increase in exposed cultures was 0.4±0.1°C; temperature controls were performed at 37°C and 37.4°C.

ばく露1

主たる特性
周波数 50 Hz
タイプ
  • magnetic field
ばく露時間 10, 30, 60 or 90 min
ばく露装置
ばく露の発生源/構造
チャンバの詳細 a pair of Helmholtz coils placed opposite to each other; surfaces of the culture plates were parallel to the force lines of the magnetic field
Sham exposure A sham exposure was conducted.
パラメータ
測定量 種別 Method Mass 備考
磁束密度 1 mT - 測定値 - -

ばく露2

主たる特性
周波数 50 Hz
タイプ
  • magnetic field
ばく露時間 6 h or 12 h
ばく露装置
ばく露の発生源/構造
  • E1と同じ装置
Sham exposure A sham exposure was conducted.
パラメータ
測定量 種別 Method Mass 備考
磁束密度 0.4 mT - - - -

Reference articles

  • Varani K et al. (2012): [ラットの脳のアデノシン受容体に対するパルス電磁界ばく露の影響]
  • Ongaro A et al. (2012): [電磁界(EMF)およびアデノシン受容体はヒト骨関節炎の滑膜線維芽細胞におけるプロスタグランジンE2およびサイトカインの放出を変化させる]
  • De Mattei M et al. (2009): [ウシ滑膜線維芽細胞内のプロスタグランジンE2放出を抑制するアデノシン類似体および電磁界]

ばく露を受けた生物:

方法 影響評価項目/測定パラメータ/方法

研究対象とした生物試料:
調査の時期:
  • ばく露後

研究の主なアウトカム(著者による)

The data revealed that exposure of cerebellar granule cells to extremely low frequency magnetic fields significantly increased sodium currents of voltage-gated sodium ion channels in a time- and intensity-dependent manner. The voltage gated sodium channel steady-state activation curve, but not the steady-state inactivation curve, was significantly shifted towards hyperpolarization by the magnetic field exposure.
Increases in intracellular arachidonic acid, prostaglandin E2 and phosphorylated protein kinase A levels in cerebellar granule cells were observed following magnetic field exposure. In addition, the magnetic field exposure significantly enhanced the enzyme activity of phospholipase A2 but not of COX-1 or COX-2.
The voltage gated sodium channel 1.2 subunit protein on the granular cell membrane was increased, but the total expression levels of 1.2 subunit protein were not affected after the magnetic field exposure indicating an insertion of new sodium ion channels into the membrane.
Cyclooxygenase inhibitors and prostaglandin E2 receptor antagonists were able to eliminate the magnetic field-induced increase in phosphorylated protein kinase A and sodium current. A protein kinase A antagonist significantly attenuated the magnetic field-induced increase in sodium current. Administration of db-cAMP (a cAMP analog) produced a significant increase of sodium current. Thus, these data support the hypothesis that cAMP/protein kinase A pathway is involved in the effect of magnetic field exposure on sodium current.
These findings demonstrated that the neuronal sodium current was significantly increased by extremely low frequency magnetic field exposure via a "phospholipase A2-arachidonic acid-prostaglandin E2- prostaglandin E2 receptor-protein kinase A" signaling pathway.

研究の種別:

研究助成

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