Figure 6From: CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Nav1.8 sodium channels in dorsal root ganglion neurons CCL2 increases tetrodotoxin-resistant Na + current amplitude and Na v 1.8 mRNA through activating the phosphatidylinositol-3 kinase/Akt pathway. (A) Tetrodotoxin (TTX)-insensitive sodium currents were evoked from a holding potential (VH) of −80 mV to step potentials ranging from −20 mV to 20 mV. In the presence of ERK 1/2 inhibitor U0126 (20 μM), chemokine CC chemokine ligand 2 (CCL2) preincubation greatly increased the magnitude of TTX-resistant Na+ currents in a small dorsal root ganglion (DRG) sensory neuron. Pretreating small-diameter DRG neurons with 5 nM CCL2 did not augment the amplitude of TTX-resistant sodium currents in the presence of phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 (10 μM) or Akt inhibitor IV (1 μM). (B) Pretreating small-diameter DRG neurons with 5 nM CCL2 increased the density of TTX-insensitive sodium Na+ currents recorded at −20 mV. PI3K inhibitor LY294002 or Akt inhibitor IV almost completely inhibited CCL2 enhancement of TTX-resistant Na+ currents. Each bar shows the mean ± standard error (SE) value of 10 neurons. (C) Pretreating DRG neurons with 5 nM CCL2 for 24 to 36 hours significantly increased the mRNA level of Nav1.8. PI3K inhibitor LY294002 or Akt inhibitor IV significantly inhibited CCL2 upregulation of Nav1.8 mRNA expression. Each bar represents the mean ± SE value of five experiments. *P <0.01 compared with control neurons.Back to article page