Transient receptor potential canonical 3 (TRPC3) is required for IgG immune complex-induced excitation of the rat dorsal root ganglion neurons

Lintao Qu, Yumei Li, Xinghua Pan, Pu Zhang, Robert H. LaMotte, Chao Ma

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic pain may accompany immune-related disorders with an elevated level of serum IgG immune complex (IgG-IC), but the underlying mechanisms are obscure. We previously demonstrated that IgG-IC directly excited a subpopulation of dorsal root ganglion (DRG) neurons through the neuronal Fc-gamma receptor I (FcγRI). This might be a mechanism linking IgG-IC to pain and hyperalgesia. The purpose of this study was to investigate the signaling pathways and transduction channels activated downstream of IgG-IC and FcγRI. In whole-cell recordings, IgG-IC induced a nonselective cation current (I IC) in the rat DRG neurons, carried by Ca 2+ and Na +. The I IC was potentiated or attenuated by, respectively, lowering or increasing the intracellular Ca 2+ buffering capacity, suggesting that this current was regulated by intracellular calcium. Single-cell RT-PCR revealed that transient receptor potential canonical 3 (TRPC3) mRNA was always coexpressed with FcγRI mRNA in the same DRG neuron. Moreover, ruthenium red (a general TRP channel blocker), BTP2 (a general TRPC channel inhibitor), and pyrazole-3 (a selective TRPC3 blocker) each potently inhibited the I IC. Specific knockdown of TRPC3 using small interfering RNA attenuated the IgG-IC-induced Ca 2+ response and the I IC. Additionally, the I IC was blocked by the tyrosine kinase Syk inhibitor OXSI-2, the phospholipase C (PLC) inhibitor neomycin, and either the inositol triphosphate (IP 3) receptor antagonist 2-aminoethyldiphenylborinate or heparin. These results indicated that the activation of neuronal FcγRI triggers TRPC channels through the Syk-PLC-IP 3 pathway and that TRPC3 is a key molecular target for the excitatory effect of IgG-IC on DRG neurons.

Original languageEnglish (US)
Pages (from-to)9554-9562
Number of pages9
JournalJournal of Neuroscience
Volume32
Issue number28
DOIs
StatePublished - Jul 11 2012
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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