TY - JOUR
T1 - Activity-dependent expression of inositol 1,4,5-trisphosphate receptor type 1 in hippocampal neurons
AU - Cai, Weihua
AU - Hisatsune, Chihiro
AU - Nakamura, Kyoko
AU - Nakamura, Takeshi
AU - Inoue, Takafumi
AU - Mikoshiba, Katsuhiko
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/5/28
Y1 - 2004/5/28
N2 - There are several lines of evidence showing that synaptic activity regulates the level of expression of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in neurons. In this study, we examined the effect of chronic activity blockade on the localization and level of IP3R1 expression in cultured hippocampal neurons. We found that chronic blockade of NMDA receptors (NMDARs), one of the major Ca2+-permeable ion channels, increased the number of neurons that express a high level of IP 3R1 without any apparent changes in its intracellular localization. Interestingly, this up-regulation was time-dependent; there was no clear change in IP3R1 expression level up to day 5 of the NMDAR blockade, but expression increased at day 6, and the increased expression level persisted for at least a week. The up-regulation of IP3R1 depended on transcription and protein synthesis and required cAMP-dependent protein kinase activity. Moreover, although most of the control neurons did not respond to the metabotropic glutamate receptor (mGluR) stimulation, the 2-amino-5-phosphonopentanoic acid-treated neurons with high IP3R1 expression became sensitive to mGluR stimulation. Furthermore, we also found that hippocampal neurons transiently overexpressing green fluorescent protein-tagged IP3R1 released Ca2+ in response to mGluR and muscarinic acetylcholine receptor stimulation. These findings suggested that chronic NMDAR blockade increased the IP3R1 expression and enhanced sensitivity to mGluR stimulation. The change in IP3R1 expression level in response to alteration of synaptic activity may be an important determinant of the sensitivity of Ca2+ stores to G-protein-coupled receptor stimulation and would help to maintain intracellular Ca2+ homeostasis in hippocampal neurons.
AB - There are several lines of evidence showing that synaptic activity regulates the level of expression of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in neurons. In this study, we examined the effect of chronic activity blockade on the localization and level of IP3R1 expression in cultured hippocampal neurons. We found that chronic blockade of NMDA receptors (NMDARs), one of the major Ca2+-permeable ion channels, increased the number of neurons that express a high level of IP 3R1 without any apparent changes in its intracellular localization. Interestingly, this up-regulation was time-dependent; there was no clear change in IP3R1 expression level up to day 5 of the NMDAR blockade, but expression increased at day 6, and the increased expression level persisted for at least a week. The up-regulation of IP3R1 depended on transcription and protein synthesis and required cAMP-dependent protein kinase activity. Moreover, although most of the control neurons did not respond to the metabotropic glutamate receptor (mGluR) stimulation, the 2-amino-5-phosphonopentanoic acid-treated neurons with high IP3R1 expression became sensitive to mGluR stimulation. Furthermore, we also found that hippocampal neurons transiently overexpressing green fluorescent protein-tagged IP3R1 released Ca2+ in response to mGluR and muscarinic acetylcholine receptor stimulation. These findings suggested that chronic NMDAR blockade increased the IP3R1 expression and enhanced sensitivity to mGluR stimulation. The change in IP3R1 expression level in response to alteration of synaptic activity may be an important determinant of the sensitivity of Ca2+ stores to G-protein-coupled receptor stimulation and would help to maintain intracellular Ca2+ homeostasis in hippocampal neurons.
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U2 - 10.1074/jbc.M313296200
DO - 10.1074/jbc.M313296200
M3 - Article
C2 - 15016804
AN - SCOPUS:2542481903
VL - 279
SP - 23691
EP - 23698
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 22
ER -