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Circulation Research
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Circulation Research. 2008;102:164-176
doi: 10.1161/CIRCRESAHA.107.165324
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(Circulation Research. 2008;102:164.)
© 2008 American Heart Association, Inc.


Review

The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the KATP Channel

Michael A. Burke, R. Kannan Mutharasan, Hossein Ardehali

From the Division of Cardiology, Feinberg Cardiovascular Institute, Northwestern University, Chicago, Ill.

Correspondence to Hossein Ardehali, MD, PhD, Tarry 12-725, 303 E Chicago Ave, Chicago, IL 60611. E-mail h-ardehali{at}northwestern.edu

This Review is part of a thematic series on ABC Transporters in the Cardiovascular System, which includes the following articles:

ATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease

The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the KATP Channel
Jack F. Oram Guest Editor

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 (KATP). KATP is widely expressed in nearly all tissues of higher organisms and couples cellular energy status to membrane potential. KATP is particularly important in the regulation of insulin secretion from pancreatic β-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 KATP channel, and its role in cardiovascular disease.


Key Words: sulfonylurea receptor • SUR2 • ATP-binding cassette (ABC) protein • KATPmyocardium




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