ATP-sensitive inward rectifier potassium channel containing sulfonylurea receptor 2 (KATP (SUR2))

ATP-sensitive potassium (KATP) channels containing the sulfonylurea receptor 2 (SUR2) subunit are hetero-octameric complexes that function as metabolic sensors, coupling intracellular ATP/ADP ratios to membrane potential (UniProt: P57071). These channels consist of four pore-forming inward rectifier potassium subunits (typically Kir6.1 or Kir6.2) and four regulatory SUR2 subunits encoded by the ABCC9 gene (PubMed: 22634751). SUR2 exists in two major splice variants: SUR2A, which is primarily expressed in cardiac and skeletal muscle, and SUR2B, which is found in vascular smooth muscle and non-vascular tissues (PubMed: 9154451). In the cardiovascular system, activation of these channels leads to hyperpolarization, resulting in vasodilation and protection against ischemic injury. Mutations in ABCC9 are associated with Cantu syndrome, a rare multisystem disorder, and forms of dilated cardiomyopathy (PubMed: 22634752). Therapeutic agents targeting SUR2 include potassium channel openers like minoxidil and nicorandil, used for hypertension and angina, while sulfonylureas can inhibit these channels, potentially impacting cardiovascular responses to stress (StatPearls: NBK542243).

Other names

ABCC9-containing KATP channelSulfonylurea receptor 2-containing KATP channelCardiac KATP channelVascular KATP channelATP-binding cassette sub-family C member 9-containing channel

Potassium channel openers (KCOs) bind to the SUR2 regulatory subunit to stabilize the open state of the channel, causing potassium efflux and membrane hyperpolarization. Conversely, sulfonylureas act as antagonists by binding to the SUR subunit to close the channel, though SUR2-containing channels typically require higher concentrations for inhibition than SUR1-containing pancreatic channels.