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dc.contributor.author Jeong, Jin-Young -
dc.contributor.author Kweon, Hae-Jin -
dc.contributor.author Suh, Byung-Chang -
dc.date.available 2017-05-11T01:34:29Z -
dc.date.created 2017-04-10 -
dc.date.issued 2016-04 -
dc.identifier.issn 1016-8478 -
dc.identifier.uri http://hdl.handle.net/20.500.11750/1547 -
dc.description.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. -
dc.language English -
dc.publisher Korean Society for Molecular and Cellular Biology -
dc.title Dual Regulation of R-Type Ca(V)2.3 Channels by M-1 Muscarinic Receptors -
dc.type Article -
dc.identifier.doi 10.14348/molcells.2016.2292 -
dc.identifier.scopusid 2-s2.0-84983567669 -
dc.identifier.bibliographicCitation Molecules and Cells, v.39, no.4, pp.322 - 329 -
dc.identifier.kciid ART002100369 -
dc.description.isOpenAccess TRUE -
dc.subject.keywordAuthor Ca(V)2.3 channel -
dc.subject.keywordAuthor Danio rerio voltage-sensitive phosphatase (Dr-VSP) -
dc.subject.keywordAuthor M-1 muscarinic receptor -
dc.subject.keywordAuthor PI(4,5)P-2 -
dc.subject.keywordAuthor Pseudojanin -
dc.subject.keywordPlus PROTEIN-KINASE-C -
dc.subject.keywordPlus CALCIUM-CHANNEL -
dc.subject.keywordPlus CA2+ CHANNELS -
dc.subject.keywordPlus N-TYPE -
dc.subject.keywordPlus ION CHANNELS -
dc.subject.keywordPlus MODULATION -
dc.subject.keywordPlus CURRENTS -
dc.subject.keywordPlus IDENTIFICATION -
dc.subject.keywordPlus PI(4,5)P-2 -
dc.subject.keywordPlus PIP2 -
dc.citation.endPage 329 -
dc.citation.number 4 -
dc.citation.startPage 322 -
dc.citation.title Molecules and Cells -
dc.citation.volume 39 -
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Department of Brain Sciences Laboratory of Brain Signal and Synapse Research 1. Journal Articles

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