Early developmental changes in intracellular Ca2+ stores in rat brain

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 - Jan 1 1999

Fingerprint

Cyclic ADP-Ribose
Calcium-Transporting ATPases
Rats
Brain
Microsomes
Synaptosomes
Inhibitory Concentration 50
Adenosine Triphosphate
Gene expression
Neurons
Tail
Switches
Pumps
Gene Expression
Amino Acids

Keywords

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

Cite this

@article{d0c9caa9bbef4728a0742266a1f05f28,
title = "Early developmental changes in intracellular Ca2+ stores in rat brain",
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.",
keywords = "Ca release, Ca store, Ca uptake, Ca-ATPase, Neurons, Thapsigargin",
author = "Singh, {Ashok K}",
year = "1999",
month = "1",
day = "1",
doi = "10.1016/S1095-6433(99)00046-X",
language = "English (US)",
volume = "123",
pages = "163--172",
journal = "Comparative biochemistry and physiology. Part A, Molecular & integrative physiology",
issn = "1095-6433",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Early developmental changes in intracellular Ca2+ stores in rat brain

AU - Singh, Ashok K

PY - 1999/1/1

Y1 - 1999/1/1

N2 - 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.

AB - 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.

KW - Ca release

KW - Ca store

KW - Ca uptake

KW - Ca-ATPase

KW - Neurons

KW - Thapsigargin

UR - http://www.scopus.com/inward/record.url?scp=0032995331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032995331&partnerID=8YFLogxK

U2 - 10.1016/S1095-6433(99)00046-X

DO - 10.1016/S1095-6433(99)00046-X

M3 - Article

C2 - 10425736

AN - SCOPUS:0032995331

VL - 123

SP - 163

EP - 172

JO - Comparative biochemistry and physiology. Part A, Molecular & integrative physiology

JF - Comparative biochemistry and physiology. Part A, Molecular & integrative physiology

SN - 1095-6433

IS - 2

ER -