ATP-sensitive potassium channel containing Sulfonylurea receptor 1 (KATP (SUR1))

The ATP-sensitive potassium (KATP) channel containing the Sulfonylurea receptor 1 (SUR1) is a hetero-octameric protein complex that serves as a vital metabolic sensor in various tissues, most notably the pancreatic beta cells. It is composed of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, which are members of the ATP-binding cassette (ABC) transporter family (UniProt P48048). The channel's primary biological function is to couple the metabolic state of the cell, specifically the ATP/ADP ratio, to its electrical activity; an increase in ATP leads to channel closure, membrane depolarization, and the triggering of insulin secretion (StatPearls, "Physiology, Adenosine Triphosphate Sensitive Potassium Channels"). Dysregulation of this channel is central to the pathogenesis of several metabolic disorders, including neonatal diabetes mellitus and congenital hyperinsulinism, resulting from gain-of-function or loss-of-function mutations in the ABCC8 or KCNJ11 genes (PubMed, PMID: 24553142). Pharmacologically, the SUR1 subunit is the target for sulfonylureas and glinides, which act as channel blockers to stimulate insulin release in patients with type 2 diabetes (NIH, PubChem). Conversely, potassium channel openers like diazoxide target SUR1 to keep the channel open and inhibit insulin release in conditions of hyperinsulinism. Additionally, SUR1-containing channels in the central nervous system are involved in neuroprotection and the regulation of neuronal excitability during metabolic stress.

Other names

KATP channelSulfonylurea receptor 1 complexABCC8/KCNJ11 channelKir6.2/SUR1 channelPancreatic KATP channel

Inhibition of the channel (closure) by sulfonylureas and glinides leads to membrane depolarization and insulin release; activation of the channel (opening) by diazoxide leads to hyperpolarization and inhibition of insulin release.