NF-kappaB mediated enhancement of potassium currents by the chemokine CXCL1/growth related oncogene in small diameter rat sensory neurons. 2009

Rui-Hua Yang, and Judith A Strong, and Jun-Ming Zhang
Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0531, USA. Rui-Hua.Yang@uc.edu

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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011984 Sensory Receptor Cells Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors. Nerve Endings, Sensory,Neurons, Sensory,Neuroreceptors,Receptors, Neural,Neural Receptors,Receptors, Sensory,Sensory Neurons,Sensory Receptors,Nerve Ending, Sensory,Neural Receptor,Neuron, Sensory,Neuroreceptor,Receptor Cell, Sensory,Receptor Cells, Sensory,Receptor, Neural,Receptor, Sensory,Sensory Nerve Ending,Sensory Nerve Endings,Sensory Neuron,Sensory Receptor,Sensory Receptor Cell
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015221 Potassium Channels Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits. Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D054360 Chemokine CXCL1 A CXC chemokine with specificity for CXCR2 RECEPTORS. It has growth factor activities and is implicated as a oncogenic factor in several tumor types. CXCL1 Chemokine,Chemokine (C-X-C Motif) Ligand 1,GROalpha Protein,Gro-alpha Protein,Growth-Related Oncogene alpha Protein,MGSA-alpha Chemokine,Melanoma Growth Stimulatory Activity, alpha Protein,Neutrophil-Activating Protein 3,CXCL1, Chemokine,Chemokine, CXCL1,Chemokine, MGSA-alpha,Gro alpha Protein,Growth Related Oncogene alpha Protein,MGSA alpha Chemokine,Neutrophil Activating Protein 3
D018408 Patch-Clamp Techniques An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. Patch Clamp Technique,Patch-Clamp Technic,Patch-Clamp Technique,Voltage-Clamp Technic,Voltage-Clamp Technique,Voltage-Clamp Techniques,Whole-Cell Recording,Patch-Clamp Technics,Voltage-Clamp Technics,Clamp Technique, Patch,Clamp Techniques, Patch,Patch Clamp Technic,Patch Clamp Technics,Patch Clamp Techniques,Recording, Whole-Cell,Recordings, Whole-Cell,Technic, Patch-Clamp,Technic, Voltage-Clamp,Technics, Patch-Clamp,Technics, Voltage-Clamp,Technique, Patch Clamp,Technique, Patch-Clamp,Technique, Voltage-Clamp,Techniques, Patch Clamp,Techniques, Patch-Clamp,Techniques, Voltage-Clamp,Voltage Clamp Technic,Voltage Clamp Technics,Voltage Clamp Technique,Voltage Clamp Techniques,Whole Cell Recording,Whole-Cell Recordings

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