TY - JOUR
T1 - ABCC8 and ABCC9
T2 - ABC transporters that regulate K+ channels
AU - Bryan, Joseph
AU - Munoz, Alvaro
AU - Zhang, Xinna
AU - Düfer, Martina
AU - Drews, Gisela
AU - Krippeit-Drews, Peter
AU - Aguilar-Bryan, Lydia
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/2
Y1 - 2007/2
N2 - 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 IR6.1/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.
AB - 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 IR6.1/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.
KW - ABCC8
KW - ABCC9
KW - Diabetes
KW - Hypoglycemia
KW - K channels
KW - KCNJ11
KW - KCNJ8
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U2 - 10.1007/s00424-006-0116-z
DO - 10.1007/s00424-006-0116-z
M3 - Review article
C2 - 16897043
AN - SCOPUS:33846658399
SN - 0031-6768
VL - 453
SP - 703
EP - 718
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
IS - 5
ER -