Sulfonylurea receptor (SUR) (SUR)

The Sulfonylurea receptor (SUR) is a critical regulatory subunit of the ATP-sensitive potassium (KATP) channel, acting as a metabolic sensor that couples the intracellular energy state to membrane potential [1, 5]. It belongs to the ATP-binding cassette (ABC) transporter superfamily, though it functions primarily as a channel modulator rather than a transporter [2]. In pancreatic beta cells, the SUR1 isoform (encoded by ABCC8) regulates insulin secretion; when glucose metabolism increases intracellular ATP, the KATP channel closes, leading to membrane depolarization and the release of insulin [3]. This receptor is the primary pharmacological target for sulfonylureas and meglitinides, which are widely used to treat type 2 diabetes by stimulating insulin secretion [4]. Mutations in the genes encoding SUR subunits are associated with clinical conditions such as congenital hyperinsulinism and neonatal diabetes [1, 2]. Additionally, the SUR2 isoform (encoded by ABCC9) is expressed in cardiac and smooth muscle, where it plays a role in vascular tone and protects the heart during metabolic stress or ischemic events [5].

Other names

ABCC8ABCC9ATP-binding cassette sub-family C member 8ATP-binding cassette sub-family C member 9SUR1SUR2Sulfonylurea receptor 1Sulfonylurea receptor 2

Sulfonylureas and meglitinides bind to the SUR subunit of the KATP channel, inducing a conformational change that closes the channel pore. This closure inhibits potassium efflux, leading to cell membrane depolarization, which subsequently opens voltage-gated calcium channels. The resulting influx of calcium ions triggers the exocytosis of insulin granules from pancreatic beta cells [3, 4]. Conversely, KATP channel openers like diazoxide bind to SUR to maintain the channel in an open state, hyperpolarizing the cell and inhibiting insulin secretion [5].