ATP-sensitive potassium channel subunit Kir6.2–Sulfonylurea receptor 1 (Kir6.2/SUR1)

The ATP-sensitive potassium channel composed of the pore-forming subunit Kir6.2 and the regulatory subunit sulfonylurea receptor 1 (SUR1) is a hetero-octameric complex that senses cellular metabolic status by coupling intracellular ATP/ADP levels to membrane excitability. Kir6.2 is a member of the inward rectifier potassium channel family, while SUR1 is an ATP-binding cassette transporter without classical transport activity, instead serving to regulate channel gating and pharmacological sensitivity. The channel is essential for regulated insulin secretion in pancreatic β-cells, linking glucose metabolism to hormone release. Mutations in either subunit disrupt glucose homeostasis and cause diseases such as diabetes or congenital hyperinsulinism. Clinically, the Kir6.2/SUR1 complex is targeted by sulfonylureas and related drugs in type 2 diabetes, while channel openers such as diazoxide are used to treat hyperinsulinemic hypoglycemia. The channel is an important therapeutic target and its molecular structure, assembly, and gating are areas of intense research, with implications for treating metabolic and neurological diseases.

Other names

KATP channel (Kir6.2/SUR1)Kir6.2–SUR1 complexATP-sensitive potassium channel (pancreatic type)KCNJ11 (Kir6.2 gene)ABCC8 (SUR1 gene)Pancreatic KATP channel

Sulfonylureas: Block (inhibit) the channel by binding SUR1 to promote insulin release; Meglitinides: Inhibit the channel at a binding site similar to sulfonylureas; Diazoxide: Opens the channel, hyperpolarizes cells, inhibits insulin secretion; Endogenous ATP binding to Kir6.2 closes the channel; MgADP binding to SUR1 opens the channel; Pharmacochaperoning: Small molecules stabilize Kir6.2 and SUR1 interactions, rescuing mutant channel trafficking