ATP-sensitive potassium channel subunit sulfonylurea receptor 2 (SUR2) (SUR2)

The ATP-sensitive potassium channel subunit sulfonylurea receptor 2 (SUR2), also known as ABCC9, is a regulatory subunit of the ATP-sensitive potassium (KATP) channel complex, belonging to the ABC transporter family. It associates with pore-forming Kir6.1 or Kir6.2 subunits to form octameric channels, primarily in vascular smooth muscle (Kir6.1/SUR2B), cardiac muscle (Kir6.2/SUR2A), and other tissues, where it couples metabolic status (ATP/ADP ratios) to membrane excitability and physiological responses like vascular tone modulation and cardioprotection. SUR2 endows the channel with sensitivity to nucleotides, sulfonylureas for inhibition, and openers like diazoxide for activation, influencing processes such as insulin secretion indirectly through related isoforms and cardiovascular function. Mutations in SUR2 or associated genes cause channelopathies like Cantú syndrome (gain-of-function leading to hypervascularity and cardiomegaly) and contribute to cardiovascular pathologies. Therapeutically, SUR2 is targeted by sulfonylureas and novel inhibitors for conditions involving inappropriate channel activity, though selectivity challenges arise due to homology with pancreatic SUR1. Structural studies reveal SUR2's TMD0 domain anchors to Kir6.x, modulating ATP/PIP2 sensitivity and gating via conformational changes in its ABC core. Efforts focus on SUR2-selective blockers to avoid off-target effects like hypoglycemia from pan-KATP inhibition.

Other names

Sulfonylurea receptor 2ABCC9

Channel inhibition by binding to high- and low-affinity sites on SUR, closing KATP channels to promote insulin secretion or vasoconstriction; MgATP-dependent enhancement of inhibition; Paradoxical stimulation at high doses for some inhibitors on Kir6.2/SUR1