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Peihan Orestes, Damir Bojadzic, JeongHan Lee, Emily Leach, Reza Salajegheh, Michael R. DiGruccio, Michael T. Nelson and Slobodan M. Todorovic Free radical signalling underlies inhibition of CaV3.2 T-type calcium channels by nitrous oxide in the pain pathway The Journal of Physiology 589

Version of Record online: 23 DEC 2010 | DOI: 10.1113/jphysiol.2010.196220

Nitrous oxide (N2O) has long been used as a pain reliever, but little is known of its targets in the body. We show that N2O 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, N2O cannot inhibit T-currents. Mice that are treated with EUK-134 to remove free radicals show little pain relief after N2O administration. This report provides new information on how N2O interacts with ion channels, helping our understanding of how this popular pain reliever works.

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