Functional interaction of neuronal Cav1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus

Sunoh Kim, Hyung Mun Yun, Ja-Hyun Baik, Chul Chung Kwang, Seung Yeol Nah, Hyewhon Rhim

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Neuronal L-type Ca2+ channels do not support synaptic transmission, but they play an essential role in synaptic activity-dependent gene expression. Cav1.2 and Cav1.3 are the two most widely expressed L-type Ca2+ channels in neurons and have different biophysical and subcellular distributions. The function of the Cav1.3 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 Cav1.3 α1 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 Cav1.3 and RyR2 in the rat hippocampus. We also demonstrate a physical association of Cav1.3 with RyR2 using co-immunoprecipitation assays. Moreover, immunocytochemistry revealed prominent co-localization between Cav1.3 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 Ca v 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 Cav1.3. These results suggest a physical and functional interaction between Cav1.3 and RyR2 and important implications of Cav1.3/RyR2 clusters in translating synaptic activity into alterations in gene expression.

Original languageEnglish
Pages (from-to)32877-32889
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number45
DOIs
Publication statusPublished - 2007 Nov 9

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L-Type Calcium Channels
Ryanodine Receptor Calcium Release Channel
Rats
Hippocampus
Assays
Gene expression
Neurons
Chemical activation
Gene Expression
Two-Hybrid System Techniques
Neurology
Transcription
RNA Interference
Immunoprecipitation
Synaptic Transmission
Yeast
Small Interfering RNA
Reverse Transcription
Amino Acid Sequence
Central Nervous System

ASJC Scopus subject areas

  • Biochemistry

Cite this

Functional interaction of neuronal Cav1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus. / Kim, Sunoh; Yun, Hyung Mun; Baik, Ja-Hyun; Kwang, Chul Chung; Nah, Seung Yeol; Rhim, Hyewhon.

In: Journal of Biological Chemistry, Vol. 282, No. 45, 09.11.2007, p. 32877-32889.

Research output: Contribution to journalArticle

Kim, Sunoh ; Yun, Hyung Mun ; Baik, Ja-Hyun ; Kwang, Chul Chung ; Nah, Seung Yeol ; Rhim, Hyewhon. / Functional interaction of neuronal Cav1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 45. pp. 32877-32889.
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