title: GABA(B) receptor-mediated ERK1/2 phosphorylation via a direct interaction with Ca(V)1.3 channels.
abstract: Neuronal L-type Ca(2+) channels play pivotal roles in regulating gene expression, cell survival, and synaptic plasticity. The Ca(V)1.2 and Ca(V)1.3 channels are 2 main subtypes of neuronal L-type Ca(2+) channels. However, the specific roles of Ca(V)1.2 and Ca(V)1.3 in L-type Ca(2+) 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(V)1.3 channel and GABA(B) receptor (GABA(B)R), we further examined the involvement of Ca(V)1.2 and Ca(V)1.3 in the GABA(B)R-mediated activation of ERK(1/2), a kinase involved in both CREB activation and synaptic plasticity. After confirming the involvement of L-type Ca(2+) channels in baclofen-induced ERK(1/2) phosphorylation, we examined a specific role of Ca(V)1.2 and Ca(V)1.3 channels in the baclofen effect. Using siRNA-mediated silencing of Ca(V)1.2 or Ca(V)1.3 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(V)1.2 or Ca(V)1.3, we found that GABA(B)R can increase ERK(1/2) phosphorylation and Ca(V)1.3 channel activity through direct interaction with Ca(V)1.3 channels. These results suggest a functional interaction between Ca(V)1.3 and GABA(B)R and important implications of Ca(V)1.3/GABA(B)R clusters for translating synaptic activity into gene expression alterations.
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Bo-Hye
authors.initials: BH
authors.lastname: Im
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003584:Cytological Techniques / Q000295:instrumentation; D018756:GABA Antagonists / Q000494:pharmacology; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; D018756:GABA Antagonists; D034741:RNA, Small Interfering; D018080:Receptors, GABA-B; C493217:calcium channel, l type beta2c subunit, rat; C093712:Cacna1d protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D001418:Baclofen; D002118:Calcium