ATP-sensitive potassium channel (KATP channel), pancreatic beta cell (KATP channel)

The ATP-sensitive potassium channel (KATP channel) in pancreatic beta cells is an octameric complex of four Kir6.2 pore-forming subunits (encoded by KCNJ11) and four sulfonylurea receptor 1 (SUR1) regulatory subunits (encoded by ABCC8), functioning as a metabolic sensor that links glucose levels to insulin secretion. Under low glucose, high ADP/ATP ratios keep channels open, maintaining hyperpolarized membrane potential; elevated glucose boosts ATP, closing channels, depolarizing the cell, opening voltage-gated calcium channels, and triggering calcium-dependent insulin exocytosis. Mutations in KCNJ11 or ABCC8 cause diseases like neonatal diabetes (reduced function) or congenital hyperinsulinism (gain-of-function), highlighting its role in glucose homeostasis. Therapeutically, sulfonylureas like glibenclamide bind SUR1 to inhibit channels and boost insulin for type 2 diabetes treatment, while diazoxide opens channels to suppress insulin in hyperinsulinism. Structural studies reveal nucleotide binding at Kir6.2 interfaces and SUR1 conformational changes coupling metabolism to gating, with challenges including hypoglycemia risk and tissue-specific isoforms.

Other names

K-ATP channelbeta-cell inward rectifier subunit (BIR)inward rectifier K(+) channel Kir6.2 (KIR6.2)ATP-sensitive inward rectifier potassium channel 11

Closure by sulfonylureas to depolarize beta cells and promote insulin release; opening by diazoxide to hyperpolarize and inhibit insulin secretion