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

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)457-465
Number of pages9
JournalJournal of Neurochemistry
Volume73
Issue number2
DOIs
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • Calcium
  • Endoplasmic reticulum
  • Neuronal survival
  • Thapsigargin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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