ATP-binding cassette sub-family C member 8 (ABCC8) (SUR1)

The ATP-sensitive potassium (KATP) channel is a hetero-octameric complex consisting of four inward-rectifier potassium channel subunits (Kir6.2) and four regulatory sulfonylurea receptor 1 (SUR1) subunits (UniProt: Q09428). SUR1, encoded by the ABCC8 gene, serves as a metabolic sensor that regulates insulin secretion from pancreatic beta cells by responding to changes in the intracellular ATP/ADP ratio (PubMed: 10592334). When blood glucose rises, increased ATP production leads to KATP channel closure, membrane depolarization, and calcium-dependent insulin release. Sulfonylurea drugs, such as glibenclamide and glipizide, bind to specific sites on the SUR1 subunit to close the channel and stimulate insulin secretion, making them vital for managing Type 2 diabetes (StatPearls: NBK519494). Mutations in the ABCC8 gene are associated with various glycemic disorders, including permanent neonatal diabetes and congenital hyperinsulinism (NCBI Gene: 6833). Beyond the pancreas, SUR1-containing channels are also found in the brain and heart, where they may play roles in neuroprotection and response to ischemia (PubMed: 15150175).

Other names

Sulfonylurea receptor 1ABCC8ATP-binding cassette sub-family C member 8MRP8PHHIHHF1ABC36

Sulfonylureas and meglitinides bind to the SUR1 regulatory subunit of the KATP channel complex, causing the pore-forming Kir6.2 subunits to close. This inhibition of potassium efflux results in membrane depolarization, which triggers the opening of voltage-gated L-type calcium channels. The resulting influx of calcium ions promotes the exocytosis of insulin-containing granules from pancreatic beta cells (PubMed: 10592334; StatPearls: NBK519494).