心臓のカルシウム電流の交感的調節は,独占的にcAMP依存のリン酸化によるものです

H C Hartzell¹, P F Méry, R Fischmeister

¹Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.

Nature

|June 13, 1991

まとめ

交感神経系とは,交感神経系である.

科学分野:

心臓病学心臓病学
分子薬理学分子薬理学
細胞生理学細胞生理学

背景:

交感神経系の刺激は,強化された電圧誘導カルシウム電流 (ICa) を通して心臓の収縮性を高めます.
この効果は,伝統的にベータアドレネルジック受容体活性化とサイクルAMP (cAMP) 依存タンパク質キナーゼA (PKA) によるカルシウムチャネルのリン酸化に起因する.
別の仮説では,ICaの急速な調節のための直接的な,膜限定のGタンパク質経路が提案されている.

研究の目的:

心臓ICaのβ-アドレネルジック刺激における直接的なGタンパク質経路とcAMP依存型リン酸化の役割を調査する.
交感神経系の心臓の収縮性に対する陽性なイノトロピック効果の背後にあるメカニズムを決定する.

主な方法:

全細胞パッチクランプ電気生理学を用いて,隔離されたカエル,ネズミ,豚の室内ミオサイトでICaを測定した.
実験では,β-アドレナジックアゴニストであるイソプロテレノールによる刺激が行われました.
cAMP依存のリン酸化阻害剤の効果が評価され,ICaの変化は収縮力の測定値と相関していた.

主要な成果:

イソプロテレノールは,すべての試験種でICaのゆっくりと単相的な増加を誘導した.
この増加は,cAMP依存型リン酸化抑制剤によって完全に廃止されました.
ICaの上昇の時間経過は,心臓の収縮力の増加を反映した.

結論:

交感神経系による心臓ICaの調節は,独占的にcAMP依存のリン酸化によって媒介されます.
これらの発見は,室内ミオサイトにおけるICa刺激のための直接的,膜限定のGタンパク質経路の存在を否定しています.
この結果は,心臓の収縮性の同情的制御を制御する分子メカニズムを明らかにしています.

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