The role of TNF-alpha/NF-kappa B pathway on the up-regulation of voltage-gated sodium channel Nav1.7 in DRG neurons of rats with diabetic neuropathy

2014 ◽  
Vol 75 ◽  
pp. 112-119 ◽  
Author(s):  
Yangliang Huang ◽  
Ying Zang ◽  
Lijun Zhou ◽  
Wenshan Gui ◽  
Xianguo Liu ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Sodium Channel ◽  
Tnf Alpha ◽  
Drg Neurons ◽  
Nf Kappa B ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

scholarly journals Functional role of the C-terminus of voltage-gated sodium channel Nav1.8

FEBS Letters ◽  
2004 ◽  
Vol 572 (1-3) ◽  
pp. 256-260 ◽  
Author(s):  
Jin-Sung Choi ◽  
Lynda Tyrrell ◽  
Stephen G Waxman ◽  
Sulayman D Dib-Hajj
Keyword(s):  
Sodium Channel ◽  
Functional Role ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
C Terminus

scholarly journals Reduction of Voltage Gated Sodium Channel Protein in DRG by Vector Mediated miRNA Reduces Pain in Rats with Painful Diabetic Neuropathy

2012 ◽  
Vol 8 ◽  
pp. 1744-8069-8-17 ◽  
Author(s):  
Munmun Chattopadhyay ◽  
Zhigang Zhou ◽  
Shuanglin Hao ◽  
Marina Mata ◽  
David J Fink
Keyword(s):  
Diabetic Neuropathy ◽  
Sodium Channel ◽  
Painful Diabetic Neuropathy ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Protein

Role of auxiliary β1-, β2-, and β3-subunits and their interaction with Nav1.8 voltage-gated sodium channel

2004 ◽  
Vol 319 (2) ◽  
pp. 531-540 ◽  
Author(s):  
Kausalia Vijayaragavan ◽  
Andrew J. Powell ◽  
Ian J. Kinghorn ◽  
Mohamed Chahine
Keyword(s):  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

scholarly journals Role of the disulfide bond on the structure and activity of μ-conotoxin PIIIA in the inhibition of NaV1.4

RSC Advances ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 668-674 ◽  
Author(s):  
Xiaoxiao Xu ◽  
Qingliang Xu ◽  
Fangling Chen ◽  
Juan Shi ◽  
Yuntian Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sodium Channel ◽  
Disulfide Bond ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Peptide Toxin ◽  
Structure And Activity

μ-Conotoxin PIIIA, a peptide toxin isolated from Conus purpurascens, blocks the skeletal muscle voltage-gated sodium channel NaV1.4 with significant potency.

scholarly journals 3’-O-Methylorobol Inhibits the Voltage-Gated Sodium Channel Nav1.7 with Anti-Itch Efficacy in A Histamine-Dependent Itch Mouse Model

2019 ◽  
Vol 20 (23) ◽  
pp. 6058 ◽  
Author(s):  
Fan Zhang ◽  
Ying Wu ◽  
Shuwen Xue ◽  
Shuangyan Wang ◽  
Chunlei Zhang ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sensory Neurons ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Cell Voltage ◽  
Comparable Efficacy ◽  
Drg Neurons ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Na Currents

An itch is a clinical complication that affects millions of patients. However, few treatment options are available. The voltage-gated sodium channel Nav1.7 is predominantly expressed in peripheral sensory neurons and is responsible for the rising phase of action potentials, thereby mediating nociceptive conduction. A gain-of-function mutation of Nav1.7 results in the hyperexcitability of sensory neurons and causes the inherited paroxysmal itch. Conversely, a monoclonal antibody that selectively inhibits Nav1.7 is able to effectively suppress the histamine-dependent itch in mice. Therefore, Nav1.7 inhibitors may possess the potential to relieve the itch. In the present study, using whole-cell voltage-clamp recordings, we demonstrated that 3’-O-methylorobol inhibited Na+ currents in Nav1.7-CHO cells and tetrodotoxin-sensitive Na+ currents in mouse dorsal root ganglion (DRG) neurons with IC50 (half-maximal inhibitory concentration) values of 3.46 and 6.60 μM, respectively. 3’-O-methylorobol also suppressed the tetrodotoxin-resistant Na+ currents in DRG neurons, though with reduced potency (~43% inhibition at 30 µM). 3’-O-methylorobol (10 µM) affected the Nav1.7 by shifting the half-maximal voltage (V1/2) of activation to a depolarizing direction by ~6.76 mV, and it shifted the V1/2 of inactivation to a hyperpolarizing direction by ~16.79 mV. An analysis of 3’-O-methylorobol activity toward an array of itch targets revealed that 3’-O-methylorobol was without effect on histamine H1 receptor, TRPV1, TRPV3, TRPV4, TRPC4 and TRPM8. The intrathecal administration of 3’-O-methylorobol significantly attenuated compound 48/80-induced histamine-dependent spontaneous scratching bouts and the expression level of c-fos in the nuclei of spinal dorsal horn neurons with a comparable efficacy to that of cyproheptadine. Our data illustrated the therapeutic potential for 3’-O-methylorobol for histamine-dependent itching, and the small molecule inhibition of Nav1.7 may represent a useful strategy to develop novel therapeutics for itching.

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