title: Diverse mechanisms underlying the regulation of ion channels by carbon monoxide.
abstract: Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, NO and cGMP levels, as well as regulate MAPK signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca(2+) -sensitive K(+) channels. More recent studies have revealed the ability of CO to inhibit T-type Ca(2+) channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.
authors.affiliation: Division of Cardiovascular and Diabetes Research, LIGHT, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
authors.forename: C
authors.initials: C
authors.lastname: Peers
authors.forename: J P
authors.initials: JP
authors.lastname: Boyle
authors.forename: J L
authors.initials: JL
authors.lastname: Scragg
authors.forename: M L
authors.initials: ML
authors.lastname: Dallas
authors.forename: M M
authors.initials: MM
authors.lastname: Al-Owais
authors.forename: N T
authors.initials: NT
authors.lastname: Hettiarachichi
authors.forename: J
authors.initials: J
authors.lastname: Elies
authors.forename: E
authors.initials: E
authors.lastname: Johnson
authors.forename: N
authors.initials: N
authors.lastname: Gamper
authors.forename: D S
authors.initials: DS
authors.lastname: Steele
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism* / Q000633:toxicity; D006152:Cyclic GMP / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007473:Ion Channels; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006152:Cyclic GMP