Maturation-dependent reduced responsiveness of intracellular free Ca2+ ions to repeated stimulation by N-methyl-d-aspartate in cultured rat cortical neurons

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金沢大学大学院自然科学研究科分子作用学

In contrast to other ionotropic glutamate receptors, N-methyl-d-aspartate (NMDA) receptor channels are rather stable after the simulation. Brief exposure to NMDA at 50 μM rapidly increased the fluorescence intensity for increased intracellular free Ca2+ levels in a reversible- and concentration-dependent manner in rat cortical neurons cultured for 3-15 days in vitro (DIV), while EC50 values were significantly decreased in proportion to cellular maturation from 3 to 15 DIV. Although a constant increase was persistently seen in the fluorescence throughout the sustained exposure to NMDA for 60 min irrespective of the cell maturation from 3 to 15 DIV, the second brief exposure for 5 min resulted in a less efficient increase in the fluorescence than that found after the first brief exposure for 5 min in a manner dependent on intervals between the two repetitive brief exposures. In vitro maturation significantly shortened the interval required for the reduced responsiveness to the second brief exposure, while in immature neurons prolonged intervals were required for the reduced responsiveness to the second brief exposure to NMDA. Moreover, brief exposure to NMDA led to a marked decrease in immunoreactivity to extracellular loop of NR1 subunit in cultured neurons not permeabilized in proportion to the time after washing. These results suggest that cellular maturation would facilitate the desensitization process to repeated stimulation by NMDA, without markedly affecting that to sustained stimulation, through a mechanism related to the decreased number of NMDA receptors expressed at cell surfaces in cultured rat cortical neurons. © 2006 Elsevier Ltd. All rights reserved.

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詳細情報 詳細情報について

  • CRID
    1050845760884041344
  • NII論文ID
    120000809691
  • ISSN
    01970186
  • Web Site
    http://hdl.handle.net/2297/2799
  • 本文言語コード
    en
  • 資料種別
    journal article
  • データソース種別
    • IRDB
    • CiNii Articles
    • KAKEN

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