Journal
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
Volume 453, Issue 5, Pages 703-718Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00424-006-0116-z
Keywords
ABCC8; ABCC9; KCNJ8; KCNJ11; K-ATP channels; diabetes; hypoglycemia
Categories
Funding
- NIDDK NIH HHS [DK44311, DK52771] Funding Source: Medline
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The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily. Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K+ selective pores, either K(IR)6.1/KCNJ8 or K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K+ channels found in endocrine cells, neurons, and both smooth and striated muscle. Adenine nucleotides, the major regulators of ATP-sensitive K+ (K-ATP) channel activity, exert a dual action. Nucleotide binding to the pore reduces the activity or channel open probability, whereas Mg-nucleotide binding and/or hydrolysis in the nucleotidebinding domains of SUR antagonize this inhibitory action to stimulate channel openings. Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic beta cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes. Additionally, the subtle dysregulation of K-ATP channel activity by a KIR6.2 polymorphism has been suggested as a predisposing factor in type 2 diabetes mellitus. Studies on K-ATP channel null mice are clarifying the roles of these metabolically sensitive channels in a variety of tissues.
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