ATP-sensitive potassium channel sulfonylurea receptor 1 or 2A subunit (SUR1 or SUR2A)

The ATP-sensitive potassium channel (KATP channel) is a hetero-octameric ion channel critical for coupling cellular metabolic state to membrane excitability, especially in pancreatic beta cells (SUR1/Kir6.2), cardiac myocytes (SUR2A/Kir6.2), and other tissues. It consists of four pore-forming Kir6.x subunits (Kir6.1 or Kir6.2) and four regulatory sulfonylurea receptor subunits (SUR1, SUR2A, or SUR2B), with SUR1 and SUR2A being regulatory subunits from the ATP-binding cassette (ABCC) family. SUR1 and SUR2A mediate metabolic and pharmacological regulation of channel activity; ATP and ADP bind and modulate gating, while drugs like sulfonylureas and channel openers target the SUR subunit to manage diseases like diabetes and cardiovascular conditions. Mutations in SUR subunits underlie rare forms of diabetes, hyperinsulinism, and some cardiomyopathies. The channel is a validated therapeutic target exploited by several classes of approved drugs.

Other names

Sulfonylurea receptor 1 (SUR1)Sulfonylurea receptor 2A (SUR2A)ABCC8 (for SUR1)ABCC9 (for SUR2A)KATP channel regulatory subunitSUR1/SUR2A subunit of KATP channel

Sulfonylureas and meglitinides block (inhibit) the channel by binding to SUR1/SUR2A, leading to closure of the potassium channel, membrane depolarization, and insulin release (for beta cell/SUR1). KATP channel openers (e.g., diazoxide) activate the channel by binding to SUR1/SUR2A, keeping the channel open so the cell does not depolarize.