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 (I-Ca) in small-diameter dorsal root ganglion (DRG) neurons, but the intracellular signaling cascade underlying MrgC agonist-induced inhibition of HVA I-Ca 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 I-Ca by JHU58 (0.001-100 nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1 mu M), 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 I-Ca in MrgA3-eGFP+ neurons by JHU58 (100 nM) was partially reduced by pretreatment with a G(beta gamma) blocker (gallein, 100 mu M). However, applying a depolarizing prepulse and blocking the G(alpha i) and G(alpha s) pathways with pertussis toxin (PTX) (0.5 mu g/mL) and cholera toxin (CTX) (0.5 mu g/mL), respectively, had no effect. These findings suggest that activation of MrgC11 may inhibit HVA I-Ca in mouse DRG neurons through a voltage-independent mechanism that involves activation of the PLC, but not G(alpha i) or G(alpha s), pathway. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
基金：
NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS70814, NS54791]; Johns Hopkins Blaustein Pain Research Fund; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81428008]; [NS26363]
通讯机构：[1]Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Ctr Sensory Biol, Baltimore, MD 21205 USA;[7]Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21287 USA;[8]Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, 725 N Wolfe St, Baltimore, MD 21287 USA
推荐引用方式(GB/T 7714)：
Li Z.,He S. -Q.,Tseng P. -Y.,et al.THE INHIBITION OF HIGH-VOLTAGE-ACTIVATED CALCIUM CURRENT BY ACTIVATION OF MRGC11 INVOLVES PHOSPHOLIPASE C-DEPENDENT MECHANISMS[J].NEUROSCIENCE.2015,300:393-403.doi:10.1016/j.neuroscience.2015.05.043.
APA：
Li, Z.,He, S. -Q.,Tseng, P. -Y.,Xu, Q.,Tiwari, V....&Guan, Y..(2015).THE INHIBITION OF HIGH-VOLTAGE-ACTIVATED CALCIUM CURRENT BY ACTIVATION OF MRGC11 INVOLVES PHOSPHOLIPASE C-DEPENDENT MECHANISMS.NEUROSCIENCE,300,
MLA：
Li, Z.,et al."THE INHIBITION OF HIGH-VOLTAGE-ACTIVATED CALCIUM CURRENT BY ACTIVATION OF MRGC11 INVOLVES PHOSPHOLIPASE C-DEPENDENT MECHANISMS".NEUROSCIENCE 300.(2015):393-403
