title: ABCC8 and ABCC9: ABC transporters that regulate K+ channels.
abstract: 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 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 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 K(IR)6.2 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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. jbryan@bcm.tmc.edu
authors.forename: Joseph
authors.initials: J
authors.lastname: Bryan
authors.forename: Alvaro
authors.initials: A
authors.lastname: Muñoz
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhang
authors.forename: Martina
authors.initials: M
authors.lastname: Düfer
authors.forename: Gisela
authors.initials: G
authors.lastname: Drews
authors.forename: Peter
authors.initials: P
authors.lastname: Krippeit-Drews
authors.forename: Lydia
authors.initials: L
authors.lastname: Aguilar-Bryan
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000596:Amino Acids / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D044903:Congenital Hyperinsulinism / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000151:congenital; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004195:Disease Models, Animal; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011955:Receptors, Drug / Q000502:physiology*; D064233:Sulfonylurea Receptors
chemical_list: C577507:ABCC8 protein, human; C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; D000596:Amino Acids; D002395:Catecholamines; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D002118:Calcium