Roles of thapsigargin-sensitive Ca2+ stores in the survival of developing cultured neurons

Chih Jung Yao, Chii Wann Lin, Shoei Yn Lin-Shiau

研究成果: 雜誌貢獻文章同行評審

25 引文 斯高帕斯(Scopus)

摘要

The roles of the intracellular calcium pool involved in regulating the Ca2+ profile and the neuronal survival rate during development were studied by using thapsigargin (TG), a specific inhibitor of endoplasmic reticulum (ER) Ca2+-ATPase in cultured cerebellar granule neurons. Measuring the neuronal [Ca2+](i) directly in the culture medium, we found a bell-shaped curve for [Ca2+](i) versus cultured days in cerebellar granule neurons maintained in medium containing serum and 25 mM K+. The progressive increase in [Ca2+](i) of the immature granule neurons (1-4 days in vitro) was abolished by TG, which resulted in massive neuronal apoptosis. When the [K+] was lowered from 25 to 5 mM, neither the progressively increasing [Ca2+](i) nor the survival of immature granule neurons was significantly changed over 24-h incubation. Similarly, TG caused a dramatic decrease in the [Ca2+](i) and survival rate of these immature neurons when switched to 5 mM K+ medium. Following maturation, the granule neurons became less sensitive to TG for both [Ca2+](i) and neuronal survival. However, TG can protect mature granule neurons from the detrimental effect of switching to a 5 mM K+ serum- free medium by decreasing [Ca2+](i) to an even lower level than in the respective TG-free group. Based on these findings, we propose that during the immature stage, TG-sensitive ER Ca2+ATPase plays a pivotal role in the progressive increase of [Ca2+](i) which is essential for the growth and maturation of cultured granule neurons.
原文英語
頁(從 - 到)457-465
頁數9
期刊Journal of Neurochemistry
73
發行號2
DOIs
出版狀態已發佈 - 1999
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 細胞與分子神經科學

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