Sulfonylurea receptor 2B-containing ATP-sensitive potassium channel (SUR2B-KATP channel)

The Sulfonylurea receptor 2B-containing ATP-sensitive potassium channel (SUR2B-KATP) is a hetero-octameric protein complex consisting of four inwardly rectifying potassium channel subunits (typically Kir6.1 or Kir6.2) and four regulatory sulfonylurea receptor 2B (SUR2B) subunits (UniProt: P57076). It is primarily expressed in vascular and non-vascular smooth muscle cells, where it acts as a critical metabolic sensor by coupling the intracellular ATP/ADP ratio to membrane excitability (PubMed: 10484331). When intracellular ATP levels decrease or ADP levels rise, the channel opens, leading to potassium efflux and membrane hyperpolarization, which ultimately causes smooth muscle relaxation and vasodilation (PubMed: 15123942). This physiological response is essential for the regulation of vascular tone and systemic blood pressure. Mutations in the ABCC9 gene, which encodes the SUR2B subunit, are associated with Cantu syndrome and various cardiovascular disorders (NIH: GeneReviews). The channel is a significant therapeutic target for potassium channel openers (KCOs) such as minoxidil and pinacidil, which are used to treat severe or refractory hypertension (StatPearls: NBK542333). However, the clinical use of these drugs is often limited by side effects like reflex tachycardia and fluid retention resulting from potent systemic vasodilation (PubMed: 11706310).

Other names

Vascular KATP channelABCC9-containing KATP channelKir6.1/SUR2B channelKir6.2/SUR2B channelSmooth muscle ATP-sensitive potassium channel

Potassium channel openers (KCOs) bind to the SUR2B regulatory subunit, stabilizing the open conformation of the associated Kir6.x pore; this results in potassium efflux, membrane hyperpolarization, and the subsequent closure of voltage-gated calcium channels, leading to smooth muscle relaxation (PubMed: 15123942).