POTASSIUM CHANNEL OPENERS AND OTHER REGULATORS OF K-ATP CHANNELS

1. Interest in ATP-sensitive K (K-ATP) channels first arose when it wa s shown that hypoglycaemic sulphonylureas, such as glibenclamide, clos ed these channels in pancreatic beta-cells to cause insulin release. T he demonstration that certain smooth muscle relaxants (K channel opene rs) may exert their actions through opening a similar channel in vascu lar smooth muscle fuelled further investigation of these channels and their physiological role in a variety of tissue types, including vario us types of smooth muscle, cardiac and skeletal muscle and neural and endocrine organ function. 2. The K channel openers have a variety of p otential therapeutic applications, including disorders of smooth muscl e hyperreactivity, such as hypertension, and a great deal of research has focused on this field. More recently, attention has turned to the cardiac actions of these compounds and this area is discussed in detai l. One of the current problems is the lack of selectivity of K-ATP cha nnel regulators. However, there have been a number of recent encouragi ng reports suggesting that, under certain pathophysiological condition s, the action of the K channel openers may be enhanced, conferring upo n them some degree of selectivity. 3. A number of endogenous regulator s of these channels have been identified, particularly in the category of endogenous openers of these channels. At present though, the physi ological role of these channels and the endogenous regulators identifi ed, is unclear. 4. It is evident that, although advances have been mad e, much work is still required to increase our understanding and ultim ately to allow selective pharmacological manipulation of these channel s to become a therapeutic reality.