Early developmental changes in intracellular Ca2+ stores in rat brain

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Abstract

Developmental changes in intracellular Ca2+ stores in brain was studied by examining: (1) IP3- and cADPR-induced increase in [Ca2+](i) in synaptosomes; (2) Ca2+-ATPase activity and ATP-dependent 45Ca2+ uptake into Ca2+ store in ER microsomes; (3) TG-induced inhibition of Ca2+- ATPase activity and ATP-dependent 45Ca2+ uptake into Ca2+ store in ER microsomes; and (4) gene expression of Ca2+-ATPase pump in neurons obtained from brains of the new-born and the 3-week-old rats. IP3 (EC50 310 ± 8 nM, 200% maximum increase in [Ca2+](i)) and cADPR (EC50 25 ± 3 nM, greater than 170% maximum increase in [Ca2+](i)) both were potent agonist of Ca2+ release from internal stores in synaptosomes obtained from the 3- week-old rats. However, IP3 (EC50 250 ± 10 nM, 175 maximum increase in [Ca2+](i)) was a potent, but cADPR (EC50 300±20 nM, 75% maximum increase) was a poor agonist of Ca2+ release from intracellular stores in synaptosomes obtained from the new-born rats. [3H]IP3, [32p]cADPR and [3H]Ry binding in the new-born samples were significantly less than that in the 3-week-old samples. [3H]Ry binding to its receptor was more sensitive to cADPR in microsomes from the 3-week-old rats than those from the new-born rats. Microsomes from the new-born rats exhibited TG-sensitive (IC50 30 ± 4 nM) and TG-insensitive forms of Ca2+-ATPase, while microsomes from the 3- week-old rats exhibited only the TG-sensitive form of Ca2+-ATPase (5±1 nM IC50). Microsomes from the 3-week-old rats were more sensitive to TG but less sensitive to IP3, while microsomes from the new-born rats were more sensitive to IP3 but less sensitive to TG. The lower TG sensitivity of the new-born Ca2+ store may be because they poorly express a 45 amino acid C- terminal tail of Ca2+-ATPase that contains the TG regulatory sites. This site is adequately expressed in the older brain. This suggests that: (1) the new-born brain contains fully operational IP3 pathway but poorly developed cADPR pathway, while the older brain contains both IP3 and cADPR pathways; and (2) a developmental switch occurs in the new-born Ca2+-ATPase as a function of maturity.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalComparative Biochemistry and Physiology - A Molecular and Integrative Physiology
Volume123
Issue number2
DOIs
StatePublished - Jun 1999

Keywords

  • Ca release
  • Ca store
  • Ca uptake
  • Ca-ATPase
  • Neurons
  • Thapsigargin

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