脳虚血への Na^+-Ca^<2+> アンチポーター応答とグリア/ニューロン死 Response of Na^+-Ca^<2+> antiporter to ischemia and glial/neuronal death

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Brain ischemia produces morphologic and biochemical alterations in astrocytes. This mini-review summarizes astrocytic responses to brain ischemia including our studies on the neuronal and astrocytic Na<SUP>+</SUP>-Ca<SUP>2+</SUP> exchanger (NCX). NCX is considered to cause Ca<SUP>2+</SUP> efflux (forward mode) or Ca<SUP>2+</SUP> influx (reverse mode), depending on the electrochemical gradient of Na<SUP>+</SUP> across the plasma membranes and membrane potential. We demonstrated that NCX is present in cultured neurons and astrocytes and that there are differences in their properties and distribution ratio of the isoforms between neurons and astrocytes. We also found that Ca<SUP>2+</SUP> depletion followed by reperfusion with Ca<SUP>2+</SUP>-containing medium caused cell death in cultured astrocytes (Call paradox-like injury), but not in neurons. The study, carried out by the use of a specific antisense oligomer, provides direct evidence that Ca<SUP>2+</SUP> paradoxlike injury is mediated by NCX in the reverse mode. The injury was attenuated by inhibitors of the Na<SUP>+</SUP>-Ca<SUP>2+</SUP> exchanger, heat shock protein and the calcineurin inhibitor FK506. In a preliminary experiment, we found that brain ischemia decreases the mRNA level of NCX in the hippocampus. Further studies on activation and cell injury of astrocytes will contribute to development of new drugs that modulate the function of astrocytes.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 111(1), 13-20, 1998-01-01

    公益社団法人 日本薬理学会

参考文献:  52件中 1-52件 を表示

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10008181891
  • NII書誌ID(NCID)
    AN00198335
  • 本文言語コード
    JPN
  • 資料種別
    REV
  • ISSN
    00155691
  • NDL 記事登録ID
    4382493
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z19-247
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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