RT Journal Article
SR Electronic
T1 Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8250
OP 8260
DO 10.1523/JNEUROSCI.1800-07.2007
VO 27
IS 31
A1 Nelson, Michael T.
A1 Woo, Jiwan
A1 Kang, Ho-Won
A1 Vitko, Iuliia
A1 Barrett, Paula Q.
A1 Perez-Reyes, Edward
A1 Lee, Jung-Ha
A1 Shin, Hee-Sup
A1 Todorovic, Slobodan M.
YR 2007
UL http://www.jneurosci.org/content/27/31/8250.abstract
AB 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.