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The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms.
Li, Z; He, S-Q; Tseng, P-Y; Xu, Q; Tiwari, V; Yang, F; Shu, B; Zhang, T; Tang, Z; Raja, S N; Wang, Y; Dong, X; Guan, Y.
Affiliation
  • Li Z; The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • He SQ; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • Tseng PY; The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • Xu Q; The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • Tiwari V; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • Yang F; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • Shu B; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Wuhan 430030, China.
  • Zhang T; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
  • Tang Z; Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu 210023, China.
  • Raja SN; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
  • Wang Y; Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Dong X; The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21287, USA. Electronic address: xdong2@jhmi.edu.
  • Guan Y; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA. Electronic address: yguan1@jhmi.edu.
Neuroscience ; 300: 393-403, 2015 Aug 06.
Article in En | MEDLINE | ID: mdl-26022362
ABSTRACT
High-voltage-activated (HVA) calcium channels play an important role in synaptic transmission. Activation of Mas-related G-protein-coupled receptor subtype C (MrgC; mouse MrgC11, rat homolog rMrgC) inhibits HVA calcium current (ICa) in small-diameter dorsal root ganglion (DRG) neurons, but the intracellular signaling cascade underlying MrgC agonist-induced inhibition of HVA ICa in native DRG neurons remains unclear. To address this question, we conducted patch-clamp recordings in MrgA3-eGFP-wild-type mice, in which most MrgA3-eGFP(+) DRG neurons co-express MrgC11 and can be identified for recording. We found that the inhibition of HVA ICa by JHU58 (0.001-100nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1µM), but not by its inactive analog (U73343) or vehicle. Further, in rats that had undergone spinal nerve injury, pretreatment with intrathecal U73122 nearly abolished the inhibition of mechanical hypersensitivity by intrathecal JHU58. The inhibition of HVA ICa in MrgA3-eGFP(+) neurons by JHU58 (100nM) was partially reduced by pretreatment with a Gßγ blocker (gallein, 100µM). However, applying a depolarizing prepulse and blocking the Gαi and Gαs pathways with pertussis toxin (PTX) (0.5µg/mL) and cholera toxin (CTX) (0.5µg/mL), respectively, had no effect. These findings suggest that activation of MrgC11 may inhibit HVA ICa in mouse DRG neurons through a voltage-independent mechanism that involves activation of the PLC, but not Gαi or Gαs, pathway.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Type C Phospholipases / Calcium Channels / Receptors, G-Protein-Coupled / Ganglia, Spinal / Neurons Type of study: Prognostic_studies Limits: Animals Language: En Journal: Neuroscience Year: 2015 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Type C Phospholipases / Calcium Channels / Receptors, G-Protein-Coupled / Ganglia, Spinal / Neurons Type of study: Prognostic_studies Limits: Animals Language: En Journal: Neuroscience Year: 2015 Document type: Article Affiliation country: United States