The sulfonylurea receptor, an atypical ATP-binding cassette protein, and its regulation of the KATP channel.
ATP-binding cassette (ABC) proteins are highly conserved and widely expressed throughout nature and found in all organisms, both prokaryotic and eukaryotic. They mediate myriad critical cellular processes, from nutrient import to toxin efflux using the energy derived from ATP hydrolysis. Most ABC proteins mediate transport of substances across lipid membranes. However, there are atypical ABC proteins that mediate other processes. These include, but are not limited to, DNA repair (bacterial MutS), ion transport (cystic fibrosis transmembrane receptor), and mRNA trafficking (yeast Elf1p). The sulfonylurea receptor (SUR) is another atypical ABC protein that regulates activity of the potassium ATP channel (K(ATP)). K(ATP) is widely expressed in nearly all tissues of higher organisms and couples cellular energy status to membrane potential. K(ATP) is particularly important in the regulation of insulin secretion from pancreatic beta-cells and in regulating action potential duration in muscle cells. SUR is indispensable for normal channel function, and mutations in genes encoding SURs increase the susceptibility to diabetes, myocardial infarction, and heart failure. Here, we review the structure and function of ABC proteins and discuss SUR, its regulation of the K(ATP) channel, and its role in cardiovascular disease.
Burke
Michael A
MA
Division of Cardiology, Feinberg Cardiovascular Institute, Northwestern University, Chicago, Ill, USA.
Mutharasan
R Kannan
RK
Ardehali
Hossein
H
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000502:physiology*; D002318:Cardiovascular Diseases; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006801:Humans; D054086:KATP Channels / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000502:physiology*; D011487:Protein Conformation; D011955:Receptors, Drug / Q000737:chemistry* / Q000502:physiology*; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D054086:KATP Channels; C484274:KCNJ5 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors