アミオダロンの心臓の2つのコンポーネントに対する短期および長期の効果 遅延整流器のK (((+) 電流
K Kamiya1, A Nishiyama, K Yasui
1Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. kamiya@riem.nagoya-u.ac.jp
Circulation
|March 10, 2001
まとめ
アミオダロンは,治療期間によって心臓のイオンチャネルに異なる影響を及ぼします. 短期間の使用はI(Kr) を抑制し,長期間の使用はI(Ks) を減少させ,タキアリズム症の治療に影響を与える.
科学分野:
- 心臓病学 心臓病学
- 薬理学 薬理学とは
- 分子生物学は分子生物学である.
背景:
- アミオダロンは,構造的な心臓病を有する患者の生命を脅かすタキアリズム症の治療に不可欠です.
- 心臓のイオンチャネルに対する複雑な効果は,短期間の投与と長期間の投与によって異なる場合があります.
研究 の 目的:
- 短期間および長期の投与後にアミオダロンが遅延整流器のカリウム電流 (I(K)) I(Ks) とI(Kr) の2つの構成要素に与える差異的な効果を調査する.
- 本来のウサギの心臓回路とクローン化されたヒトの心臓回路に対するアミオダロンの効果を比較する.
主な方法:
- ウサギの室内ミオサイトにおける全細胞電圧クランプ技術で,I(K),I(Kr,およびI(Ks) を測定した.
- 使用された特定の阻害剤 (クロマノール293BはI(Ks),E-4031はI(Kr)).
- クローンされたHERG (I(Kr)) とKvLQT1/minK (I(Ks)) チャンネルを発現するXenopus卵細胞における評価効果.
- 長期効果を研究するために,アミオダロンを4週間にわたってウサギに投与した.
主要な成果:
- 短期的なアミオダロンは,ウサギのミオサイトで,I(Ksに最小限の効果で,I(Kr) (IC50=2.8 μmol/L) を抑制した.
- 卵細胞では,アミオダロンはHERG (I(Kr)) 電流 (IC50=38 μmol/L) を抑制したが,KvLQT1/minK (I(Ks)) 電流は抑制しなかった.
- 長期のアミオダロン治療 (4週間) は,総I (((K) を55%減少させ,I ((Kr) /I ((Ks) の比率を変更しました.
- 長期にわたるアミオダロン治療の後,ERG,KVLQT1,またはminKのmRNAレベルに重大な変化は観察されなかった.
結論:
- アミオダロンは,投与期間によってI(Kr) とI(Ks) に異なる効果を発揮する.
- 短期的なアミオダロンは主にI ((Kr)) を標的にし,抑制する.
- 長期にわたってアミオダロンを投与すると,I (((Ks)) の低下につながる.
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