کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6272032 | 1614776 | 2015 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms](/preview/png/6272032.png)
- The inhibition of HVA ICa in DRG neurons by an MrgC agonist (JHU58) was reduced by a phospholipase C inhibitor, U73122.
- Blocking the Gαi and Gαs pathways did not reduce the JHU58-induced inhibition of HVA ICa in DRG neurons.
- A depolarizing prepulse did not reduce the inhibition of HVA ICa by JHU58.
- Intrathecal U73122 reduced the inhibition of mechanical hypersensitivity by JHU58 in nerve-injured rats.
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 (0.001-100 nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1 μM), 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 (100 nM) was partially reduced by pretreatment with a Gβγ blocker (gallein, 100 μM). However, applying a depolarizing prepulse and blocking the Gαi and Gαs pathways with pertussis toxin (PTX) (0.5 μg/mL) and cholera toxin (CTX) (0.5 μg/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.
Journal: Neuroscience - Volume 300, 6 August 2015, Pages 393-403