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

The ATP-sensitive potassium (KATP) channel containing the Sulfonylurea receptor 2B (SUR2B) subunit is a hetero-octameric protein complex primarily expressed in vascular and non-vascular smooth muscle cells [1, 2]. It typically consists of four pore-forming Kir6.1 subunits and four regulatory SUR2B subunits, which are splice variants of the ABCC9 gene [1, 4]. These channels function as metabolic sensors, coupling the intracellular ATP/ADP ratio to membrane excitability; a decrease in ATP or an increase in ADP triggers channel opening, leading to potassium efflux and membrane hyperpolarization [2, 5]. This hyperpolarization closes voltage-gated calcium channels, resulting in smooth muscle relaxation and vasodilation, which makes the channel a critical regulator of vascular tone and blood pressure [1, 3]. Pharmacologically, the channel is targeted by potassium channel openers like pinacidil and minoxidil to treat hypertension and angina, while its overactivity is linked to Cantu syndrome and its dysfunction to conditions like Prinzmetal angina [1, 4]. Recent research also highlights its role in migraine pathophysiology and its potential as a target for treating patent ductus arteriosus [3, 1]. Sources: [1] nih.gov (PMC4019701, PMC10510537, PMC9421014) [2] ahajournals.org (Circulation Research, 2019) [3] mdpi.com (Cells, 2023) [4] frontiersin.org (Frontiers in Physiology, 2022) [5] oup.com (Brain, 2022)

Other names

SUR2BABCC9 splice variantVascular KATP channelSmooth muscle KATP channelKir6.1/SUR2B channelSulfonylurea receptor 2B

Potassium channel openers (KCOs) bind to the SUR2B regulatory subunit, promoting the open state of the channel. This leads to an efflux of K+ ions, hyperpolarizing the cell membrane and closing voltage-gated calcium channels, which ultimately results in smooth muscle relaxation and vasodilation. Conversely, KATP channel blockers like glibenclamide bind to the SUR subunit to inhibit channel activity, leading to membrane depolarization and vasoconstriction.