ピエゾ2は,呼吸道伸縮を感知し,肺膨張による無呼吸を媒介する
Keiko Nonomura1, Seung-Hyun Woo1, Rui B Chang2
1Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA.
Nature
|December 22, 2016
まとめ
機械的に活性化されたイオンチャネルPiezo2は呼吸に不可欠です. 新生児の呼吸不全と成人の呼吸異常は,呼吸制御におけるその役割を強調しています.
科学分野:
- 生理学
- 神経科学
- 分子生物学
背景:
- 呼吸器機能障害は幼児死亡率と成人の睡眠時無呼吸に大きく寄与する.
- 呼吸制御の正確なメカニズム,特に呼吸道感覚神経からの機械信号は,完全に理解されていません.
- これらの過程における機械的に活性化されたイオンチャネルの役割は,大部分は不明である.
研究 の 目的:
- 呼吸制御における 機械的に活性化されたイオンチャネルPiezo2の役割を調査する.
- 呼吸道感覚神経細胞におけるピエゾ2媒介メカニカル伝導の生理学的意義と分子メカニズムを解明する.
- 生まれてから成人期までの正常な呼吸に必要なPiezo2を決定する.
主な方法:
- 発達中のマウスと成人のマウスのPiezo2を除去するために,遺伝子アブレーション技術 (全般的および感覚神経特異的) を利用した.
- 成人マウスのピエゾ2発現する ヴァガル感覚神経細胞を活性化するために 光遺伝学を使用した.
- 呼吸機能の評価 肺の膨張に対するニューロンの反応 遺伝子組み換えマウスのヘリング・ブレュアー反射
主要な成果:
- Piezo2の消去は新生マウスの呼吸困難と死亡を引き起こした.
- 成人マウスのピエゾ2+ ヴァガル感覚神経細胞の光遺伝的活性化により,無呼吸が誘発された.
- 成人の感覚神経細胞におけるPiezo2の喪失は,肺の膨張反応を弱め,ヘリング・ブリュアー反射を弱め,潮量を増加させた.
結論:
- ピエゾ2は 重要な呼吸道伸縮センサーとして機能します
- 呼吸道を阻害する感覚ニューロンのピエゾ2媒介メカニカル伝導は,出生時に効果的な呼吸を確立するために不可欠です.
- この経路は成人の生涯にわたって正常な呼吸パターンを維持するために不可欠です.
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