Premium
Free radical signalling underlies inhibition of Ca V 3.2 T‐type calcium channels by nitrous oxide in the pain pathway
Author(s) -
Orestes Peihan,
Bojadzic Damir,
Lee JeongHan,
Leach Emily,
Salajegheh Reza,
DiGruccio Michael R.,
Nelson Michael T.,
Todorovic Slobodan M.
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.196220
Subject(s) - chemistry , reactive oxygen species , pharmacology , catalase , nitrous oxide , superoxide dismutase , voltage dependent calcium channel , nitric oxide , t type calcium channel , biochemistry , hydrogen peroxide , biophysics , calcium , antioxidant , medicine , biology , organic chemistry
Non‐technical summary Nitrous oxide (N 2 O) has long been used as a pain reliever, but little is known of its targets in the body. We show that N 2 O indirectly inhibits T‐type calcium channels through free radical reactions. These reactions depend on a histidine residue on the channel that binds metal ions. If we prevent this histidine from binding metals, N 2 O cannot inhibit T‐currents. Mice that are treated with EUK‐134 to remove free radicals show little pain relief after N 2 O administration. This report provides new information on how N 2 O interacts with ion channels, helping our understanding of how this popular pain reliever works.