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Dual Regulation of R-Type Ca(V)2.3 Channels by M-1 Muscarinic Receptors

Title
Dual Regulation of R-Type Ca(V)2.3 Channels by M-1 Muscarinic Receptors
Authors
Jeong, JY[Jeong, Jin-Young]Kweon, HJ[Kweon, Hae-Jin]Suh, BC[Suh, Byung-Chang]
DGIST Authors
Jeong, JY[Jeong, Jin-Young]; Kweon, HJ[Kweon, Hae-Jin]; Suh, BC[Suh, Byung-Chang]
Issue Date
2016-04
Citation
Molecules and Cells, 39(4), 322-329
Type
Article
Article Type
Article
Keywords
AnimalAnimalsCalcium Channels, R-TypeCav2.3 ChannelCell MembraneChemistryDanio Rerio Voltage-Sensitive Phosphatase (Dr-VSP)Drug EffectsGene Expression RegulationHEK293 Cell LineHEK293 CellsHumanHumansM1 Muscarinic ReceptorMembrane PotentialMembrane PotentialsMetabolismMuscarinic M1 ReceptorPatch-Clamp TechniquePatch-Clamp TechniquesPhorbol 13 Acetate 12 MyristatePhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol 4,5 BisphosphatePI(4,5)P2Protein Kinase C (PKC)PseudojaninReceptor, Muscarinic M1Tetradecanoylphorbol AcetateZebrafishZebrafish ProteinZebrafish Proteins
ISSN
1016-8478
Abstract
Voltage-gated Ca2+ (CaV) channels are dynamically modulated by G protein-coupled receptors (GPCR). The M1 muscarinic receptor stimulation is known to enhance CaV2.3 channel gating through the activation of protein kinase C (PKC). Here, we found that M1 receptors also inhibit CaV2.3 currents when the channels are fully activated by PKC. In whole-cell configuration, the application of phorbol 12- myristate 13-acetate (PMA), a PKC activator, potentiated CaV2.3 currents by ~two-fold. After the PMA-induced potentiation, stimulation of M1 receptors decreased the CaV2.3 currents by 52 ± 8%. We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is responsible for the muscarinic suppression of CaV2.3 currents by using two methods: the Danio rerio voltagesensing phosphatase (Dr-VSP) system and the rapamycininduced translocatable pseudojanin (PJ) system. First, dephosphorylation of PI(4,5)P2 to phosphatidylinositol 4- phosphate (PI(4)P) by Dr-VSP significantly suppressed CaV2.3 currents, by 53 ± 3%. Next, dephosphorylation of both PI(4)P and PI(4,5)P2 to PI by PJ translocation further decreased the current by up to 66 ± 3%. The results suggest that CaV2.3 currents are modulated by the M1 receptor in a dual mode-that is, potentiation through the activation of PKC and suppression by the depletion of membrane PI(4,5)P2. Our results also suggest that there is rapid turnover between PI(4)P and PI(4,5)P2 in the plasma membrane. © The Korean Society for Molecular and Cellular Biology. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/1547
DOI
10.14348/molcells.2016.2292
Publisher
Korean Society for Molecular and Cellular Biology
Related Researcher
Files:
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Collection:
Brain and Cognitive SciencesETC1. Journal Articles


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