Oxidation of ion channels in the aging nervous system

Ion channelsareintegralmembraneproteinsthatallowpassivediffusionofionsacross membranes. Inneuronsandinotherexcitablecells,theharmoniouscoordinationbetween the numeroustypesofionchannelsshapeandpropagateelectricalsignals.Increased accumulation ofreactiveoxidativespecies(ROS),andsubsequentoxidationofproteins, including ionchannels,isahallmarkfeatureofagingandmaycontributetocellfailureas a result.InthisreviewwediscusstheeffectsofROSonthreemajortypesofionchannels of thecentralnervoussystem,namelythepotassium(Kþ), calcium(Ca2þ) andsodium (Naþ) channels.WeexaminetwogeneralmechanismsthroughwhichROSaffection channels: viadirectoxidationofspecific residuesandviaindirectinterferenceofpathways that regulatethechannels. The overallstatusofthepresentstudiesindicatesthattheinteractionofionchannels with ROSismultimodalandpervasiveinthecentralnervoussystemandlikelyconstitutes a generalmechanismofagingsusceptibility.