ABCC8 and ABCC9: ABC transporters that regulate K+ channels.

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Bryan J, Munoz A, Zhang X, Dufer M, Drews G, Krippeit-Drews P, Aguilar-Bryan L

ABCC8 and ABCC9: ABC transporters that regulate K+ channels.

Pflugers Arch. 2007 Feb;453(5):703-18. Epub 2006 Aug 8.

PubMed ID

16897043 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
ATP	ATP-binding cassette sub-family C member 8	Protein	Humans	Unknown	Not Available	Details
ATP	ATP-binding cassette sub-family C member 9	Protein	Humans	Unknown	Not Available	Details