QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 1, 2007, 27(31):8250-8260; doi:10.1523/JNEUROSCI.1800-07.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Nelson, M. T. Articles by Todorovic, S. M. Search for Related Content PubMed PubMed Citation Articles by Nelson, M. T. Articles by Todorovic, S. M.

 Previous Article  |  Next Article 

Cellular/Molecular
Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels

Michael T. Nelson,^1,4 Jiwan Woo,⁷ Ho-Won Kang,^5,6 Iuliia Vitko,² Paula Q. Barrett,² Edward Perez-Reyes,^2,4 Jung-Ha Lee,^5,6 Hee-Sup Shin,⁷ and Slobodan M. Todorovic^1,3,4

Departments of ¹Anesthesiology, ²Pharmacology, and ³Neuroscience and ⁴Neuroscience Graduate Program, University of Virginia Health System, Charlottesville, Virginia 22908, ⁵Department of Life Science and ⁶Interdisciplinary Program of Biotechnology, Sogang University, Shinsu-Dong, Seoul 121-742, Korea, and ⁷Center for Neural Science, Korea Institute of Science and Technology, Hawolgok-Dong, Seongbuk-Gu, Seoul 136-791, Korea

Correspondence should be addressed to Slobodan M. Todorovic, Department of Anesthesiology, University of Virginia Health System, Box 800710, Charlottesville, VA 22908. Email: st9d{at}virginia.edu

Recent studies have demonstrated an important role for T-type Ca²⁺ channels (T-channels) in controlling the excitability of peripheral pain-sensing neurons (nociceptors). However, the molecular mechanisms underlying the functions of T-channels in nociceptors are poorly understood. Here, we demonstrate that reducing agents as well as endogenous metal chelators sensitize C-type dorsal root ganglion nociceptors by chelating Zn²⁺ ions off specific extracellular histidine residues on Ca_v3.2 T-channels, thus relieving tonic channel inhibition, enhancing Ca_v3.2 currents, and lowering the threshold for nociceptor excitability in vitro and in vivo. Collectively, these findings describe a novel mechanism of nociceptor sensitization and firmly establish reducing agents, as well as Zn²⁺, Zn²⁺-chelating amino acids, and Zn²⁺-chelating proteins as endogenous modulators of Ca_v3.2 and nociceptor excitability.

Key words: dorsal root ganglion; action potential; C-fiber; calcium current; nociception; pain; sensitization; zinc

---

Received April 20, 2007; revised June 19, 2007; accepted June 20, 2007.

Correspondence should be addressed to Slobodan M. Todorovic, Department of Anesthesiology, University of Virginia Health System, Box 800710, Charlottesville, VA 22908. Email: st9d{at}virginia.edu

This article has been cited by other articles:

				M. M. Jagodic, S. Pathirathna, P. M. Joksovic, W. Lee, M. T. Nelson, A. K. Naik, P. Su, V. Jevtovic-Todorovic, and S. M. Todorovic Upregulation of the T-Type Calcium Current in Small Rat Sensory Neurons After Chronic Constrictive Injury of the Sciatic Nerve J Neurophysiol, June 1, 2008; 99(6): 3151 - 3156. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help