WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience MBF Stereo Investigator
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, March 19, 2008, 28(12):3190-3201; doi:10.1523/JNEUROSCI.4403-07.2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Hudmon, A.
Right arrow Articles by Dib-Hajj, S. D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hudmon, A.
Right arrow Articles by Dib-Hajj, S. D.

 Previous Article  |  Next Article 

Cellular/Molecular
Phosphorylation of Sodium Channel Nav1.8 by p38 Mitogen-Activated Protein Kinase Increases Current Density in Dorsal Root Ganglion Neurons

Andy Hudmon,1,2,3 Jin-Sung Choi,1,2,3 Lynda Tyrrell,1,2,3 Joel A. Black,1,2,3 Anthony M. Rush,1,2,3 Stephen G. Waxman,1,2,3 and Sulayman D. Dib-Hajj1,2,3

1Department of Neurology and 2Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, and 3Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516

Correspondence should be addressed to Dr. Sulayman D. Dib-Hajj, The Center for Neuroscience and Regeneration Research, 127A, Building 34, Veterans Affairs Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516. Email: sulayman.dib-hajj{at}yale.edu

The sensory neuron-specific sodium channel Nav1.8 and p38 mitogen-activated protein kinase are potential therapeutic targets within nociceptive dorsal root ganglion (DRG) neurons in inflammatory, and possibly neuropathic, pain. Nav1.8 channels within nociceptive DRG neurons contribute most of the inward current underlying the depolarizing phase of action potentials. Nerve injury and inflammation of peripheral tissues cause p38 activation in DRG neurons, a process that may contribute to nociceptive neuron hyperexcitability, which is associated with pain. However, how substrates of activated p38 contribute to DRG neuron hyperexcitability is currently not well understood. We report here, for the first time, that Nav1.8 and p38 are colocalized in DRG neurons, that Nav1.8 within DRG neurons is a substrate for p38, and that direct phosphorylation of the Nav1.8 channel by p38 regulates its function in these neurons. We show that direct phosphorylation of Nav1.8 at two p38 phospho-acceptor serine residues on the L1 loop (S551 and S556) causes an increase in Nav1.8 current density that is not accompanied by changes in gating properties of the channel. Our study suggests a mechanism by which activated p38 contributes to inflammatory, and possibly neuropathic, pain through a p38-mediated increase of Nav1.8 current density.

Key words: channel modulation; SB203580; kinase inhibitor; inflammation; nociception; anisomycin; stress

Received Oct. 26, 2006; revised Feb. 7, 2008; accepted Feb. 7, 2008.

Correspondence should be addressed to Dr. Sulayman D. Dib-Hajj, The Center for Neuroscience and Regeneration Research, 127A, Building 34, Veterans Affairs Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516. Email: sulayman.dib-hajj{at}yale.edu






-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-