ATP-sensitive potassium channel sulfonylurea receptor subunit (SUR) (SUR)

The ATP-sensitive potassium (K_ATP) channel sulfonylurea receptor (SUR) subunit is a critical regulatory component of the K_ATP channel complex, which couples cellular metabolic status to membrane excitability [1, 5]. It belongs to the ATP-binding cassette (ABC) transporter superfamily and exists in two primary forms: SUR1 (encoded by ABCC8), predominantly found in pancreatic beta cells and neurons, and SUR2 (encoded by ABCC9), found in cardiac, skeletal, and smooth muscle [1, 8, 12]. By sensing the intracellular ATP/ADP ratio, the SUR subunit modulates the opening and closing of the pore-forming Kir6.x subunits [5, 13]. In pancreatic beta cells, an increase in the ATP/ADP ratio leads to channel closure, triggering membrane depolarization and insulin secretion [5, 18]. This mechanism makes the SUR subunit a primary therapeutic target for metabolic disorders; sulfonylurea drugs and meglitinides inhibit the receptor to stimulate insulin release in type 2 diabetes, while potassium channel openers like diazoxide activate it to treat hyperinsulinism [3, 9, 10]. Mutations in the SUR subunits are linked to various genetic conditions, including neonatal diabetes, congenital hyperinsulinism, and Cantú syndrome [12, 16, 19].

Other names

SURSUR1SUR2ABCC8ABCC9Sulfonylurea receptor 1Sulfonylurea receptor 2ATP-binding cassette sub-family C member 8ATP-binding cassette sub-family C member 9ABC36ABC37PHHIHHF1

Sulfonylureas and meglitinides bind to the SUR subunit, inhibiting the K_ATP channel, which leads to membrane depolarization and insulin secretion. Potassium channel openers bind to the SUR subunit to stabilize the open state of the channel, causing hyperpolarization and inhibiting cellular activity [3, 9, 10].