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NF-kappaB Mediated Enhancement of Potassium Currents by the Chemokine CXCL1/growth Related Oncogene in Small Diameter Rat Sensory Neurons

NF-kappaB Mediated Enhancement of Potassium Currents by the Chemokine CXCL1/growth Related Oncogene in Small Diameter Rat Sensory Neurons

Rui-Hua Yang, Judith A Strong, Jun-Ming Zhang

Mol Pain. 2009 May 28;5:26.

PMID: 19476648

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413115	GRO/KC (CXCL1) from rat			Price

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