BRAIN and NERVE－神経研究の進歩63巻7号

2011年07月発行

増大特集 神経筋接合部―基礎から臨床まで

神経系の機能，遺伝子発現および発生をつかさどるカルシウムチャネル群

著者： 中尾章人¹ 高田宜則¹ 森泰生¹

所属機関： ¹京都大学大学院工学研究科合成・生物化学専攻分子生物化学分野

ページ範囲：P.657 - P.667

文献概要

はじめに

　生体内においてカルシウムイオン（Ca^2＋）はセカンドメッセンジャーとしてさまざまな生理応答に関与する。細胞外Ca^2＋濃度はmMのオーダーであるのに対し，定常状態の細胞内Ca^2＋濃度（［Ca^2＋］_i）は約100nMと非常に低く保たれている。［Ca^2＋］_iが上昇すると，神経伝達物質放出やシナプス可塑性，遺伝子発現を含むさまざまな生理応答が引き起こされるが，これには細胞内外の急峻な濃度勾配を利用する形質膜越えのCa^2＋流入経路が重要な役割を果たしている。Ca^2＋流入を担うCa^2＋チャネルとしては，N-methyl-D-aspartate（NMDA）受容体に代表されるようなリガンド作動性Ca^2＋チャネル，電位依存性Ca^2＋チャネル（voltage-dependent calcium channel：VDCC），non-classical Ca^2＋チャネルが存在する。細胞内のCa^2＋濃度変化に関与するオルガネラとしては，小胞体とミトコンドリアが存在する。小胞体内のCa^2＋濃度はsmooth endoplasmic reticulum Ca^2＋ ATPase（SERCA）の働きにより10～100μMと細胞質中よりも高く保たれており，Ca^2＋ストアとして働いている。このことから，小胞体からのCa^2＋放出により［Ca^2＋］_iを大きく上昇させることが可能である。Ca^2＋放出は，inositol (1,4,5)-triphosphate（IP₃）受容体とリアノジン受容体が担うことが広く知られている^1）。これに対し，ミトコンドリア内のCa^2＋濃度は細胞質中と同程度の100nM程度であると見積もられているが^2，3），細胞に刺激が加わるとミトコンドリアはCa^2＋を蓄えることができ，Ca^2＋バッファリング能を有することが知られている^4，5）。このように［Ca^2＋］_iは，形質膜と小胞体，ミトコンドリアの3者を介したCa^2＋の流出入により，時空間的に厳密に制御されている。

　本稿では，神経系における，細胞膜の脱分極によって活性化されるVDCCと，non-classical Ca^2＋チャネルとして働くtransient receptor potential（TRP）を介したシグナル伝達について，最新の知見を踏まえて概説する。

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