強化されたサルコプラズマ網膜のCa2+漏れとNa+-Ca2+交換器の機能の増加が,慢性心房細動の患者における遅延後の脱極化の原因となっている
Niels Voigt1, Na Li, Qiongling Wang
1Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Germany.
Circulation
|March 30, 2012
まとめ
心房細動の患者では,Ca2+/カルモジュリン依存タンパク質キナーゼII (CaMKII) とライオノジン受容体 (RyR2) によって引き起こされる,サルコプラズマ網膜のCa2+) 漏れが増加すると,危険な心拍が促進されます.
科学分野:
- 心臓病学 心臓病学
- 分子生物学は分子生物学である.
- 電気生理学 電気生理学
背景:
- Na(+) -Ca(2+) -交換電流 (I(NCX)) によって媒介される遅延後の脱極化 (DADs) は,心房細動 (AF) を引き起こす可能性があります.
- AF患者におけるDADの背後にあるメカニズムは不明である.
研究 の 目的:
- 慢性AF (cAF) 患者におけるDADのメカニズムを調査する.
- cAFにおけるサルコプラズマ網膜 (SR) のCa2+ハンドリングとRyR2機能における分子変化を特定する.
主な方法:
- ウェスタン・ブロット,パッチ・クランプ,Fluo-3画像を用いた対照およびcAF患者からの右心房サンプル分析.
- SR Ca ((2+) リーク,RyR2 開放確率,およびタンパク質リン酸化の測定.
- CaMKIIとタンパク質キナーゼAの薬理学的抑制.
- 変異したRyR2リン酸化を持つノックインマウスでの研究.
主要な成果:
- cAFの患者は,ダイアストリックSR Ca(2+) リークが著しく増加し,RyR2開く確率は増加しました.
- 特定の部位でのCaMKIIの発現と活性,およびRyR2のリン酸化の増加はcAFで観察されました.
- CaMKIIの阻害により,SR Ca(2+) リークと自発的な Ca(2+) 放出が減少しました.
- I ((NCX) はcAFでアップレギュレーションされ,ダイアストリック[Ca ((2+) ](i) -電圧カップリングの加減が増加しました.
結論:
- CaMKII-ハイパーリン酸化RyR2経由による強化されたSR Ca(2+) 漏れは,caFにおけるDADの重要なメカニズムである.
- 増加したI (NCX) と上昇したダイアストリック[Ca (NC2+) ] (i) -電圧カップリング・ゲインはAF促進に寄与する.
関連する概念動画
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