慢性的なアルファアドレネルゲン受容体刺激は,心筋細胞の収縮性現象型をin vitroで調節する
1Cardiovascular Section, Boston University Medical Center, Myocardial Biology Unit and Cardiac Muscle Research Laboratory, Boston University School of Medicine, Boston, MA 02118, USA.
Circulation
|November 1, 2000
まとめ
心臓細胞における慢性アルファアドレネルジック刺激は,カルシウムを処理する重要なタンパク質を減少させ,収縮性を低下させます. この交感性活動変化はまた,ナトリウム-カルシウム交換器を活性化させ,ナトリウムに対する細胞の反応を変化させます.
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.
- 細胞生理学 細胞生理学
背景:
- 心不全は,心筋の収縮機能不全と,交感活動の増加を含む.
- 慢性アルファアドレナージック刺激が心筋細胞現象型に与える影響を調査した.
研究 の 目的:
- 慢性アルファアドレナージック刺激が心筋細胞の分子および収縮性特性をどのように変化させるかを決定する.
主な方法:
- 成人ラットの心室筋細胞を培養し,48時間アルファアドレナージック刺激にさらした.
- 重要なイオントランスポーター (SERCA,RyR,NCX) のmRNAおよびタンパク質レベルを測定した.
- 細胞内カルシウムトランジエントと刺激後の肌細胞縮小を評価した.
主要な成果:
- アルファアドレナージック刺激により,サルコプラズマ網膜のCa(2+) -ATPaseおよびCa(2+) 放出チャネル発現が著しく低下しました.
- mRNAとタンパク質の両方のレベルでのNa(+) -Ca(2+) 交換体の発現の増加.
- 細胞内カルシウム振幅の低下,筋細胞の縮小,およびリラックス時間の延長が観察されました.
結論:
- 慢性的なアルファアドレナージック刺激は,SERCAとRyRをダウンレギュレーションし,筋細胞の収縮性が低下する.
- Na(+) - Ca(2+) 交換器のアップレギュレーションにより,細胞内ナトリウムレベルに対する感受性が高まります.
- これらの分子変化は,交感性ストレス下にある心筋細胞の収縮状態の変化に寄与する.
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