ATP-sensitive potassium channels.

ATP-sensitive potassium (K-ATP) channels link membrane excitability to metabolism. They are regulated by intracellular nucleotides and by other factors including membrane phospholipids, protein kinases and phosphatases. K-ATP channels comprise octamers of four Kir6 pore-forming subunits associated with four sulphonylurea receptor subunits. The exact subunit composition differs between the tissues in which the channels are expressed, which include pancreas, cardiac, smooth and skeletal muscle and brain. K-ATP channels are targets for antidiabetic sulphonylurea blockers, and for channel opening drugs that are used as antianginals and antihypertensives. This review focuses on non-pancreatic K-ATP channels. In vascular smooth muscle, K-ATP channels are extensively regulated by signalling pathways and cause vasodilation, contributing both to resting blood flow and vasodilator-induced increases in flow. Similarly, K-ATP channel activation relaxes smooth muscle of the bladder, gastrointestinal tract and airways. In cardiac muscle, sarcolemmal K-ATP channels open to protect cells under stress conditions such as ischaernia or exercise, and appear central to the protection induced by ischaernic preconditioning (IPC). Mitochondrial K-ATP channels are also strongly implicated in IPC, but clarification of their exact role awaits information on their molecular structure. Skeletal muscle K-ATP channels play roles in fatigue and recovery, K+ efflux, and glucose uptake, while neuronal channels may provide ischaernic protection and underlie the glucose-responsiveness of hypothalamic neurones. Current therapeutic considerations include the use of K-ATP openers to protect cardiac muscle, attempts to develop openers selective for airway or bladder, and the question of whether block of extra-pancreatic K-ATP channels may cause adverse cardiovascular side-effects of sulphonylureas.