Publication Date:
2014-04-15
Description:
Chemokine (C-C motif) ligand (CCL2) contributes to the inflammation-induced neuropathic pain through activating voltage-gated sodium channel-mediated nerve impulse conduction, but the underlying mechanism is currently unknown. Our study aimed to investigate whether Protein Kinase C (PKC)-NF-κB is involved in CCL2-induced regulation of voltage-gated sodium Nav1.8 currents and expression. Dorsal root ganglion (DRG) neurons were prepared from adult male Sprague-Dawley rats and incubated with various concentration of CCL2 for 24 hours. Whole-cell patch-clamps were performed to record the Nav1.8 currents in response to the induction by CCL2. After being pretreated with 5 nM and10 nM CCL2 for 16 h, CCR2 and Nav1.8 expression significantly increased and the peak currents of Na v 1.8 elevated from the baseline 46.53 ± 4.53 pA/pF to 64.28 ± 3.12 pA/pF following 10 nM CCL2 (P〈0.05). Compared to the control, significant change in Na v 1.8 current density was observed when the CCR2 inhibitor INCB3344 (10 nM) was applied. Furthermore, inhibition of PKC by AEB071 significantly eliminated CCL2-induced elevated Nav1.8 currents. In vitro PKC kinase assays and autoradiograms suggested that Nav1.8 within DRG neurons was a substrate of PKC and direct phosphorylation of the Na v 1.8 channel by PKC regulates its function in these neurons. Moreover, p65 expression was significantly higher in CCL2-induced neurons (P〈0.05), and was reversed by treatment with INCB3344 and AEB071. PKC-NF-κB are involved in CCL2-induced elevation of Na v 1.8 current density by promoting the phosphorylation of Na v 1.8 and its expression.
Print ISSN:
0144-8463
Electronic ISSN:
1573-4935
Topics:
Biology
,
Chemistry and Pharmacology
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