遅いナトリウム電流は,心室再極化に対するIKr阻害の反転速度依存効果に貢献します
1Department of Biology, Gilead Sciences, 1651 Page Mill Road, Palo Alto, CA 94304, USA. lin971@yahoo.com
Circulation
|April 13, 2011
まとめ
遅いナトリウム電流 (遅いI ((Na)) の抑制は,I ((Kr)) 阻害剤のプロアリズム反転速度の依存性を軽減します. この発見は,遅いI (Na) がブラディカルディアに関連した心室不律症に寄与することを示唆しています.
科学分野:
- 心臓病学 心臓病学
- 電気生理学 電気生理学
- 薬理学 薬理学とは
背景:
- I(Kr) 阻害薬の逆速依存 (RRD) は,アクションポテンシャル持続時間 (APD) とビート・トゥ・ビート・レポラライゼーション (BVR) の変動性を増加させ,プロアリズム症を引き起こす.
- この現象における内生的な遅いナトリウム電流 (遅いI(Na)) の役割は完全に理解されていません.
研究 の 目的:
- 内在の遅発I (Na) を阻害することで,I (Kr) 阻害のRRDとプロアリズム効果を弱めることができるかどうかを判断する.
- ブラディカルディアに関連した心室不律症に遅いI (Na) の寄与を調査する.
主な方法:
- モノフェーシックAPD (MAPD) とBVRは,さまざまなサイクルの長さでペースを設定された雌ウサギの心臓で測定されました.
- 心臓は,遅いI (Na) 阻害剤 (テトロドトキシン,ラノラジン) を併用したI (Kr) 阻害剤 (E-4031,d-ソタロール) を投与した.
- カーディオミオサイトにおける遅いI (Na) と計算モデルも分析した.
主要な成果:
- I ((Kr) 阻害剤は,MAPD ((90)) とBVRを増加させ,ペースが遅い場合により大きな効果を示した.
- 遅いI (Na) 阻害は,MAPDのRRDを著しく弱め,BVRを軽減し,Torsade de pointesを廃止しました.
- 遅いI ((Na) は,遅いI ((Na) 阻害により,遅いI ((Na) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)) 阻害により,遅いI ((Na)).
結論:
- 内生遅発I (Na) は,I (Kr) 阻害剤誘発のAPDとBVRのRRDに寄与する.
- 遅いI (Na) の阻害は,前動脈リズム効果を軽減し,ブラディカルディアに関連した心室動脈不律の治療標的である可能性があります.
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