The Pharmacology of ATP-Sensitive K⁺ Channels (K_ATP)

ATP-sensitive K⁺ channels (K_ATP) are inwardly-rectifying potassium channels, broadly expressed throughout the body. K_ATP is regulated by adenine nucleotides, characteristically being activated by falling ATP and rising ADP levels thus playing an important physiological role by coupling cellular metabolism with membrane excitability. The hetero-octameric channel complex is formed of 4 pore-forming inward rectifier Kir6.x subunits (Kir6.1 or Kir6.2) and 4 regulatory sulfonylurea receptor subunits (SUR1, SUR2A, or SUR2B). These subunits can associate in various tissue-specific combinations to form functional K_ATP channels with distinct electrophysiological and pharmacological properties. K_ATP channels play many important physiological roles and mutations in channel subunits can result in diseases such as disorders of insulin handling, cardiac arrhythmia, cardiomyopathy, and neurological abnormalities. The tissue-specific expression of K_ATP channel subunits coupled with their rich and diverse pharmacology makes K_ATP channels attractive therapeutic targets in the treatment of endocrine and cardiovascular diseases.