title: Stromal Cell-Derived Factor 1 Increases Tetrodotoxin-Resistant Sodium Currents Nav1.8 and Nav1.9 in Rat Dorsal Root Ganglion Neurons via Different Mechanisms.
abstract: Stromal cell-derived factor 1 (SDF-1)/chemokine CXC motif ligand 12 (CXCL12), a chemokine that is upregulated in dorsal root ganglion (DRG) during chronic pain models, has recently been found to play a central role in pain hypersensitivity. The purpose of present study is to investigate the functional impact of SDF-1 and its receptor, chemokine CXC motif receptor 4 (CXCR4), on two TTXR sodium channels in rat DRG using electrophysiological techniques. Preincubation with SDF-1 caused a concentration-dependent increase of Nav1.8 and Nav1.9 currents amplitudes in acutely isolated small diameter DRG neurons in short-term culture. As to Nav1.9, changes in current density and kinetic properties of Nav1.9 current evoked by SDF-1(50 ng/ml) was eliminated by CXCR4 antagonist AMD3100 and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. The increase in Nav1.9 current was also blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of Gi/o but not Gs subunits. As to Nav1.8, inhibitors (AMD3100, PTX, CTX, LY294002) used in present study didn't inhibit the increased amplitude of Nav1.8 current and shifted activation curve of Nav1.8 in a hyperpolarizing direction in the presence of SDF-1 (50 ng/ml). In conclusion, our data demonstrated that SDF-1 may excite primary nociceptive sensory neurons by acting on the biophysical properties of Nav1.8 and Nav1.9 currents but via different mechanisms.
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China.
authors.forename: Yong-Yan
authors.initials: YY
authors.lastname: Fan
authors.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China. yliu919@gmail.com.
authors.forename: Yan-Hong
authors.identifier: http://orcid.org/0000-0001-9315-9245
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China. wdmi1962@163.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Mi
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000502:physiology*; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; C113705:Scn11a protein, rat; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin
keywords: Dorsal root ganglion; G-protein coupled receptors; Nociception; Stromal cell-derived factor 1; Tetrodotoxin-resistant sodium channel