GABA_B receptor-mediated ERK_1/2 phosphorylation via a direct interaction with Ca_V1.3 channels

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• 作者：Bo-Hye Im^a ; ^b ; Hyewhon Rhim^a ; ^b ; ^{hrhim@kist.re.kr} ; ^{hyewhon@gmail.com}
• 关键词：L-type Ca2+ channels ; Baclofen ; Intracellular Ca2+ ; FDSS6000
• 刊名：Neuroscience Letters
• 出版年：2012
• 期刊代码：52_03043940
• 类别：neu
• 出版时间：28 March, 2012
• 卷：513
• 期：1
• 页码：89-94
• 文件大小：526 K

摘要

Neuronal L-type Ca²⁺ channels play pivotal roles in regulating gene expression, cell survival, and synaptic plasticity. The Ca_V1.2 and Ca_V1.3 channels are 2 main subtypes of neuronal L-type Ca²⁺ channels. However, the specific roles of Ca_V1.2 and Ca_V1.3 in L-type Ca²⁺ channel-mediated neuronal responses and their cellular mechanisms are poorly elucidated. On the basis of our previous study demonstrating a physical interaction between the Ca_V1.3 channel and GABA_B receptor (GABA_BR), we further examined the involvement of Ca_V1.2 and Ca_V1.3 in the GABA_BR-mediated activation of ERK_1/2, a kinase involved in both CREB activation and synaptic plasticity. After confirming the involvement of L-type Ca²⁺ channels in baclofen-induced ERK_1/2 phosphorylation, we examined a specific role of Ca_V1.2 and Ca_V1.3 channels in the baclofen effect. Using siRNA-mediated silencing of Ca_V1.2 or Ca_V1.3 messenger, we determined the relevance of each channel subtype to baclofen-induced ERK_1/2 phosphorylation in a mouse hippocampal cell line (HT-22) and primary cultured rat neurons. In the detailed characterization of each subtype using HEK293 cells transfected with Ca_V1.2 or Ca_V1.3, we found that GABA_BR can increase ERK_1/2 phosphorylation and Ca_V1.3 channel activity through direct interaction with Ca_V1.3 channels. These results suggest a functional interaction between Ca_V1.3 and GABA_BR and important implications of Ca_V1.3/GABA_BR clusters for translating synaptic activity into gene expression alterations.