ATP-sensitive inward rectifier potassium channel subunit Kir6.2 (Kir6.2)

The **ATP-sensitive inward rectifier potassium channel subunit Kir6.2 (Kir6.2)** is the core pore-forming component of the KATP channel, structurally assembling as a tetramer in complex with four sulfonylurea receptor 1 (SUR1) regulatory subunits. This channel is a **metabolic sensor**: its activity is regulated by the intracellular ratio of ATP/ADP, PI(4,5)P2, and pharmacological agents. In pancreatic β-cells, Kir6.2/SUR1 channels close in response to high ATP (after glucose uptake), causing membrane depolarization and triggering insulin release. Mutations in Kir6.2, especially those altering ATP binding or channel gating, can cause **permanent neonatal diabetes mellitus** and related syndromes with neurological features. The channel is a well-established drug target for diabetes therapy, particularly for sulfonylurea drugs, but modulation must be carefully managed to avoid serious side effects, notably hypoglycemia[1][6][4][5][3][7]. Key scientific context: Kir6.2 provides a structural potassium pore gated by ATP and regulated allosterically by SUR1 and phosphoinositides, translating metabolic signals into electrical activity. Its function and dysfunction are central in diabetes pathophysiology and therapy[1][6][4].

Other names

Inward rectifier potassium channel subunit Kir6.2KCNJ11ATP-sensitive potassium channel subunit Kir6.2

Sulfonylureas: Bind to SUR1 to inhibit Kir6.2, close the channel, depolarize cell membrane, stimulate insulin secretion Diazoxide/openers: Stabilize open state of Kir6.2/SUR1 complex, promote hyperpolarization, inhibit insulin release Drugs may alter ATP/ADP sensitivity through effects on the nucleotide-binding pocket