Kim, Sunoh Yun, Hyung-Mun Baik, Ja-Hyun Chung, Kwang Chul Nah, Seung-Yeol Rhim, Hyewhon 2024-01-21T00:05:07Z 2024-01-21T00:05:07Z 2021-09-02 2007-11-09 0021-9258 https://pubs.kist.re.kr/handle/201004/133980 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. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC CA2+ CHANNELS NMDA RECEPTOR SKELETAL-MUSCLE GENE-EXPRESSION DIHYDROPYRIDINE RECEPTOR CREB PHOSPHORYLATION NEUROTRANSMITTER RELEASE INSULIN-SECRETION STRIATAL NEURONS BETA-CELLS Functional interaction of neuronal ca(v)1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus Article 10.1074/jbc.M701418200 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.282, no.45, pp.32877 - 32889 JOURNAL OF BIOLOGICAL CHEMISTRY 282 45 32877 32889 scie scopus 000250625400037 2-s2.0-36349037017 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article CA2+ CHANNELS NMDA RECEPTOR SKELETAL-MUSCLE GENE-EXPRESSION DIHYDROPYRIDINE RECEPTOR CREB PHOSPHORYLATION NEUROTRANSMITTER RELEASE INSULIN-SECRETION STRIATAL NEURONS BETA-CELLS Cav1.3 L-type Calcium Channel Ryanodine Receptor Type-2