Genetic Discovery of ATP-Sensitive K+ Channels in Cardiovascular Diseases

The ATP-sensitive K+ (KATP) channels are hetero-octameric protein complexes comprising 4 pore-forming (Kir6.x) subunits and 4 regulatory sulfonylurea receptor (SURx) subunits. They are prominent in myocytes, pancreatic β cells, and neurons and link cellular metabolism with membrane excitability. Using genetically modified animals and genomic analysis in patients, recent studies have implicated certain ATP-sensitive K+ channel subtypes in physiological and pathological processes in a variety of cardiovascular diseases. In this review, we focus on the causal relationship between ATP-sensitive K+ channel activity and pathophysiology in the cardiovascular system, particularly from the perspective of genetic changes in human and animal models.