Abstract
A wealth of recent studies has highlighted the diverse and important influences of carbon monoxide (CO) on cellular signaling pathways. Such studies have implicated CO, and the enzymes from which it is derived (heme oxygenases) as potential therapeutic targets, particularly (although not exclusively) in inflammation, immunity and cardiovascular disease.1 In a recent study,2 we demonstrated that CO inhibited cardiac L-type Ca(2+) channels. This effect arose due to the ability of CO to bind to mitochondria (presumably at complex IV of the electron transport chain) and so cause electron leak, which resulted in increased production of reactive oxygen species. These modulated the channel's activity through interactions with three cysteine residues in the cytosolic C-terminus of the channel's major, pore-forming subunit. Our study provided a potential mechanism for the cardioprotective effects of CO and also highlighted ion channels as a major potential target group for this gasotransmitter.