Sulfonylurea receptor 1 subunit of the ATP-sensitive potassium channel (SUR1)

SUR1 (Sulfonylurea receptor 1) is the regulatory subunit of the ATP-sensitive potassium (KATP) channel, primarily expressed in pancreatic beta cells. It forms an octameric channel complex with four Kir6.2 pore-forming subunits and four SUR1 regulatory subunits. SUR1 is a member of the ATP-binding cassette (ABC) transporter family, but unlike typical ABC transporters, it modulates ion channel activity rather than transporting substrates. It translates changes in cellular metabolism (ATP/ADP ratio) into changes in membrane excitability, controlling insulin secretion. Health and disease relevance arises from alterations in SUR1 function or expression: loss-of-function mutations lead to hyperinsulinism, while gain-of-function mutations lead to neonatal diabetes. SUR1 is the molecular target for multiple antidiabetic drugs, including sulfonylureas and meglitinides, which stimulate insulin secretion by inhibiting KATP channels. Its function as a therapeutic target is validated by its critical role in metabolic regulation and insulin release, though its modulation requires caution due to risks of hypoglycemia and off-target cardiovascular effects.

Other names

Sulfonylurea receptor 1ABCC8 (gene symbol encoding SUR1)SUR-1ATP-binding cassette sub-family C member 8KATP channel regulatory subunit

Sulfonylureas bind SUR1 and inhibit the channel, causing closure and depolarization, resulting in insulin secretion. Meglitinides similarly inhibit KATP channels via SUR1 binding to stimulate insulin release. Diazoxide opens the channel by binding SUR1, leading to hyperpolarization and reduced insulin release.