Rapid Electrical Stimulation of Contraction Modulates Gap-Junction Protein in Neonatal Rat Cultured Cardiomyocytes Involvement of Mitogen-Activated Protein Kinases and Effects of Angiotensin II-Receptor Antagonist

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  • INOUE Noriko
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine
  • OHKUSA Tomoko
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine
  • NAO Tomoko
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine
  • LEE Jong-Kook
    Department of Circulation. Research Institute of Environmental Medicine, Nagoya University
  • MATSUMOTO Tomo
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine
  • HISAMATSU Yuji
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine
  • SATOH Takashi
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine
  • YANO Masafumi
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine
  • YASUI Kenji
    Department of Circulation. Research Institute of Environmental Medicine, Nagoya University
  • KODAMA Itsuo
    Department of Circulation. Research Institute of Environmental Medicine, Nagoya University
  • MATSUZAKI Masunori
    Department of Internal Medicine II. and Digital Bio-information Medicine, Yamaguchi University School of Medicine

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Other Title
  • 新生仔ラット培養心筋細胞への高頻度電気刺激負荷によるギャップ結合蛋白発現修飾の検討　　ＭＡＰキナーゼとアンギオテンシンＩＩ受容体きっ抗薬との関連について
  • ミニ・レビュー 小西賞受賞者 新生仔ラット培養心筋細胞への高頻度電気刺激負荷によるギャップ結合蛋白発現修飾の検討 MAPキナーゼとアンギオテンシン2受容体拮抗薬との関連について
  • ミニ レビュー コニシショウ ジュショウシャ シンセイシラット バイヨウ シンキン サイボウ エ ノ コウヒンド デンキ シゲキ フカ ニ ヨル ギャップ ケツゴウ タンパク ハツゲン シュウショク ノ ケントウ MAP キナーゼ ト アンギオテンシン 2 ジュヨウタイ キッコウヤク ト ノ カンレン ニ ツイテ

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BACKGROUND The expression and distribution of gap junctions in cardiac muscle can be changed readily under a variety of pathological conditions because of dynamic turnover of connexins. The effects of rapid electrical stimulation (RES) of contraction on the gap junction remodeling are not well-understood.<br>METHODS Neonatal rat ventricular myocytes cultured for 5 days were subjected to RES at 3.0 Hz for up to 120 min.<br>RESULTS RES resulted in a significant upregulation of Cx43. Angiotensin II content was increased significantly by RES >15 min. Phosphorylated forms of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinases (JNK) and p38 mitogen-activated protein kinases (p38 MAPKs) were all increased dramatically by RES with peaks at 5-60 min. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system. Conduction velocity was increased significantly by RES for 60 to 90 min. Treatment of myocytes with losartan prevented most of these effects of RES. RES-induced upregulation of Cx43 was also prevented by specific inhibitors for ERK and p38 MAPKs.<br>CONCLUSIONS A short-term RES causes upregulation of Cx43 in cardiomyocytes and a concomitant increase of conduction velocity mainly through an autocrine action of Angiotensin II to activate ERK and p38 MAPKs.

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