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KCNJ11 tetramer:ABCC8 tetramer binds 4xATP, closing the channel

Stable Identifier
R-HSA-265682
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
Closing of Inward Rectifying, ATP-sensitive Potassium Channels (KATP channels)
Locations in the PathwayBrowser
Summation

The beta-cell ATP-sensitive potassium channel (KATP channel) comprise the tetrameric ATP-sensitive inward rectifier potassium channel 11 (KCNJ11, Kir6.2) and the tetrameric channel regulator ATP-binding cassette sub-family C member 8 (ABCC8). When the ATP/ADP ratio is high, the KCNJ11 (Kir6.2) subunit binds ATP and the channel closes. Conversely, when the ADP:ATP ratio is high, the ABCC8 (SUR1) subunit binds magnesium-ADP and the channel is open.
The KATP channels in the beta cell are inwardly rectifying (allowing potassium ions to pass out of the cell) and are partially responsible for maintaining the resting potential of the cell, about -70 mV. Closure of the KATP channels causes a depolarization (a reduction in the voltage differential) across the plasma membrane.
The antidiabetic activity of sulfonylurea drugs such as acetohexamide, tolbutamide, glipzide, glibenclamide, and glimepiride is due to their binding ABCC8 (SUR1) subunits and inhibiting potassium efflux.

Literature References
PubMed ID Title Journal Year
18346985 A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel activity and beta-cell glucose sensing is associated with type 2 diabetes in adults Diabetes 2008
16332676 A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels J Biol Chem 2006
16556766 Minireview: implication of mitochondria in insulin secretion and action Endocrinology 2006
19587354 Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel Diabetes 2009
10206966 Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP inhibition of KATP channel isoforms J Biol Chem 1999
18596924 Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations J Clin Invest 2008
17919183 Action potentials and insulin secretion: new insights into the role of Kv channels Diabetes Obes Metab 2007
11078440 Triggering and amplifying pathways of regulation of insulin secretion by glucose Diabetes 2000
10868950 Diverse roles of K(ATP) channels learned from Kir6.2 genetically engineered mice Diabetes 2000
17021801 Functional analysis of six Kir6.2 (KCNJ11) mutations causing neonatal diabetes Pflugers Arch 2006
16513675 Characterization of voltage-dependent sodium and calcium channels in mouse pancreatic A- and B-cells J Physiol 2006
10866047 Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y Diabetes 2000
17380317 Low levels of glucose transporters and K+ATP channels in human pancreatic beta cells early in development Diabetologia 2007
20086079 Inwardly rectifying potassium channels: their structure, function, and physiological roles Physiol Rev 2010
10194514 The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells J Mol Endocrinol 1999
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ATP binding activity of KCNJ11 tetramer:ABCC8:Mg2+:ADP tetramer [plasma membrane]
Physical Entity
Activity
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Orthologous Events