KATP

Potassium ATP channels (KATP channels) are a family of inwardly rectifying potassium channels that couple cellular metabolic state to membrane excitability. They form octameric complexes composed of four pore-forming Kir6.x subunits and four regulatory sulfonylurea receptor (SUR) subunits. Kir6.x creates the potassium-selective pore, while SUR modulates channel activity in response to nucleotides and pharmacological ligands. Subunit composition varies by tissue, giving rise to tissue-specific channels. In pancreatic beta cells the channel is Kir6.2 paired with SUR1, in cardiac muscle Kir6.2 with SUR2A, and in vascular smooth muscle Kir6.1 with SUR2B; some neurons express other combinations.

Mechanism: intracellular ATP binds to Kir6.x and inhibits opening, whereas MgADP binding to SUR promotes opening. Thus cellular energy state controls channel activity: high ATP tends to close, low energy or metabolic stress tends to open, producing K+ efflux and hyperpolarization. In pancreatic beta cells, closure of KATP channels leads to depolarization, Ca2+ influx, and insulin secretion; in cardiac and smooth muscle, opening of KATP channels during metabolic stress can hyperpolarize cells and reduce excitability, limiting energy demand and preserving viability.

Pharmacology: sulfonylureas (for example, glibenclamide) block SUR1-containing channels to stimulate insulin release, used in type 2 diabetes. Diazoxide opens KATP channels to suppress insulin secretion during hyperinsulinism. Other KATP openers promote vasodilation and can confer cardioprotection during ischemia.

Clinical relevance: genetic mutations in KCNJ11, ABCC8, KCNJ8, or ABCC9 alter channel function and underlie conditions such as congenital hyperinsulinism or Cantú syndrome, illustrating the channel’s role in linking metabolism with electrical activity.