NF-kappaB mediated enhancement of potassium currents by the chemokine CXCL1/growth related oncogene in small diameter rat sensory neurons

Mol Pain. 2009 May 28;5:26. doi: 10.1186/1744-8069-5-26.

Abstract

Background: Inflammatory processes play important roles in both neuropathic and inflammatory pain states, but the effects of inflammation per se within the sensory ganglia are not well understood. The cytokine growth-related oncogene (GRO/KC; CXCL1) shows strong, rapid upregulation in dorsal root ganglion (DRG) in both nerve injury and inflammatory pain models. We examined the direct effects of GRO/KC on small diameter DRG neurons, which are predominantly nociceptive. Whole cell voltage clamp technique was used to measure voltage-activated potassium (K) currents in acutely cultured adult rat small diameter sensory neurons. Fluorescently labeled isolectin B4 (IB4) was used to classify cells as IB4-positive or IB4-negative.

Results: In IB4-negative neurons, voltage-activated K current densities of both transient and sustained components were increased after overnight incubation with GRO/KC (1.5 nM), without marked changes in voltage dependence or kinetics. The average values for the slow and fast decay time constants at 20 mV were unchanged by GRO/KC. The amplitude of the fast inactivating component increased significantly with no large shifts in the voltage dependence of inactivation. The increase in K currents was completely blocked by co-incubation with protein synthesis inhibitor cycloheximide (CHX) or NF-kappaB inhibitors pyrrolidine dithiocarbamate (PDTC) or quinazoline (6-Amino-4-(4-phenoxypheny lethylamino;QNZ). In contrast, the voltage-activated K current of IB4-positive neurons was unchanged by GRO/KC. GRO/KC incubation caused no significant changes in the expression level of eight selected voltage-gated K channel genes in quantitative PCR analysis.

Conclusion: The results suggest that GRO/KC has important effects in inflammatory processes via its direct actions on sensory neurons, and that activation of NF-kappaB is involved in the GRO/KC-induced enhancement of K currents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chemokine CXCL1 / metabolism*
  • Female
  • Kinetics
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / metabolism*

Substances

  • Chemokine CXCL1
  • NF-kappa B
  • Potassium Channel Blockers
  • Potassium Channels