フォスフォレマン媒介によるNa/K-ATPaseの活性化は,マウス室内ミオサイトにおけるβ-アドレネルジック刺激中にNa[i]とイノトロピック状態を制限する
Sanda Despa1, Amy L Tucker, Donald M Bers
1Department of Physiology, Loyola University Chicago, Maywood, Ill, USA.
Circulation
|March 26, 2008
まとめ
フォスフォレマン (PLM) リン酸化は心臓のNa/K-ATPase (NKA) を刺激し,交感活性化中に細胞内ナトリウムとカルシウム上昇を温める. これはマウスの心臓の収縮性や不律を制限する.
科学分野:
- 心血管生理学 心血管の生理学
- 分子心臓病学 分子心臓病学
- 細胞電気生理学 細胞電気生理学
背景:
- 心臓のNa/K-ATPase (NKA) は,細胞内ナトリウム ([Na](i) を調節し,細胞内カルシウム ([Ca](i)) とNa/Ca交換による収縮性に影響を与えます.
- NKAに関連したトランスメブランタンパク質であるフォスフォレマン (PLM) のリン酸化は,β-アドレナジック誘発のNKA刺激を媒介する.
研究 の 目的:
- ベータアドレナジック活性化中のPLMリン酸化が[Na]{i}の上昇,Caの一時的な振幅を制限し,マウス室内ミオサイトで不律を誘発するかどうかを調査する.
主な方法:
- ワイルドタイプ (WT) とPLMノックアウト (PLM-KO) のマウス室内ミオサイトを使用した.
- 測定された細胞内ナトリウム ([Na](i)) とサルコプラズマ網膜のカルシウム含有量.
- フィールド刺激とイソプロテレノールでミオサイトを刺激する.
主要な成果:
- WTミオサイトでは,イソプロテレノールは,PLMリン酸化経由でNKAを刺激することで[Na]を減少させた.
- PLM-KOミオサイトは,WTと比較して,イソプロテレノール刺激で[Na](i) とより大きなCaトランジント幅,およびサルコプラズマ網膜のCa含有量のより大きな増加を示した.
- PLM-KOミオサイトは,自発的なCaトランジントと収縮の増加を示した.
結論:
- PLMのリン酸化と,その後のNKAの刺激は,同情反応の重要な構成要素である.
- このメカニズムは[Na](i) と細胞カルシウム負荷の上昇を抑制する.
- これは,カルシウム過負荷によって引き起こされる不律を制限するのに役立つかもしれません.
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