We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels.
- Authors
Nelson, Michael T.; Jiwan Woo; Ho-Won Kang; Vitko, Iuliia; Barrett, Paula Q.; Perez-Reyes, Edward; Jung-Ha Lee; Hee-Sup Shin; Todorovic, Slobodan M.
- Abstract
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 Cav3.2 T-channels, thus relieving tonic channel inhibition, enhancing Cav3.2 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 Cav3.2 and nociceptor excitability.
- Subjects
NOCICEPTORS; CALCIUM channels; ZINC; CHELATES; AMINO acids
- Publication
Journal of Neuroscience, 2007, Vol 27, Issue 31, p8250
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1800-07.2007