, Volume 453, Issue 5, pp 703-718
Date: 08 Aug 2006

ABCC8 and ABCC9: ABC transporters that regulate K+ channels


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 KIR6.1/KCNJ8 or KIR6.2/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+ (KATP) 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 nucleotide-binding 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 β cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes. Additionally, the subtle dysregulation of KATP channel activity by a KIR6.2 polymorphism has been suggested as a predisposing factor in type 2 diabetes mellitus. Studies on KATP channel null mice are clarifying the roles of these metabolically sensitive channels in a variety of tissues.