ヒトの慢性心房細動における,Gタンパク質に結合した内向修正K (((+)) 流 (I (((K,ACh)) のダウンレギュレーションの分子基礎:GIRK4 mRNAの減少は,I (((K,ACh))
1Department of Pharmacology, University of Technology, Dresden, Germany. dobrev@rcs.urz.tu-dresden.de
Circulation
|November 21, 2001
まとめ
ヒトにおける慢性心房細動 (AF) は,Gタンパク質に結合した内向き矯正K ((+)) 流 (I ((K,ACh)) をダウンレギュレーションし,内向き矯正K ((+)) 流 (I ((K1)) をアップレギュレーションする. AFにおけるこの電気的改造は,ミオサイトを高速度に適応させます.
科学分野:
- 心臓病学 心臓病学
- 電気生理学 電気生理学
- 分子生物学は分子生物学である.
背景:
- パラシンパティック神経系は,心房細動 (AF) の病原性に関与しています.
- 慢性AFにおけるGタンパク質結合の内向整合K ((+) 流 (I ((K,ACh)) の役割は不明である.
研究 の 目的:
- 慢性AFの患者からのヒト心房筋細胞におけるI(K,ACh) とそのGIRK4サブユニットの変化を調査する.
- AFにおける変化イオン電流の機能的関連性を検証する.
主な方法:
- 隔離されたヒト心房筋細胞における電気生理学的記録.
- 競争的な逆転写ポリメラーゼ連鎖反応を用いたGIRK4およびKir2.1mRNAレベルの定量分析.
- アクションポテンシャルの持続時間と,マスカリン受容体刺激に対する反応の評価.
主要な成果:
- I(K,ACh) 密度はAFミオサイトで約50%減少し,GIRK4 mRNA.が減少した.
- 内向きの整形K (((+) 電流 (I (((K1)) 密度はAFで倍増し,Kir2.1 mRNA.が増加しました.
- AFではアクションポテンシャル持続時間が短縮され,マスカリン受容体媒介の縮小が弱まった.
結論:
- 慢性AFは,ヒトの心房におけるI ((K,ACh)) の転写上調節とI ((K,ACh)) の下調調節につながる.
- これらのイオンチャネルの変化は,アクションポテンシャルに対するムスカリン受容体効果を弱める.
- 耳頭筋細胞は,慢性的に高い速度に適応するためにI ((K,ACh) を低調調節し,電気的改造効果に対抗する.
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