期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 45, 页码 32877-32889出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M701418200
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资金
- Ministry of Education, Science & Technology (MoST), Republic of Korea [2E19650] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [핵06A3301, 과C6A2204] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Neuronal L-type Ca2+ channels do not support synaptic transmission, but they play an essential role in synaptic activity-dependent gene expression. Ca(v)1.2 and Ca(v)1.3 are the two most widely expressed L-type Ca2+ channels in neurons and have different biophysical and subcellular distributions. The function of the Ca(v)1.3 L-type Ca2+ channel and its cellular mechanisms in the central nervous system are poorly understood. In this study, using a yeast two-hybrid assay, we found that the N terminus of the rat Ca(v)1.3 alpha(1) subunit interacts with a partial N-terminal amino acid sequence of ryanodine receptor type 2 (RyR2). Reverse transcription-PCR and Western blot assays revealed high expression of both Ca(v)1.3 and RyR2 in the rat hippocampus. We also demonstrate a physical association of Ca(v)1.3 with RyR2 using co-immunoprecipitation assays. Moreover, immunocytochemistry revealed prominent co-localization between Ca(v)1.3 and RyR2 in hippocampal neurons. Depolarizing cells by an acute treatment of a high concentration of KCl (high-K, 60 mM) showed that the activation of L-type Ca2+ channels induced RyR opening and led to RyR-dependent Ca2+ release, even in the absence of extracellular Ca2+. Furthermore, we found that RyR2 mRNA itself is increased by long term treatment of high-K via activation of L-type Ca2+ channels. These acute and long term effects of high-K on RyRs were selectively blocked by small interfering RNA-mediated silencing of Ca(v)1.3. These results suggest a physical and functional interaction between Ca(v)1.3 and RyR2 and important implications of Ca(v)1.3/RyR2 clusters in translating synaptic activity into alterations in gene expression.
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