Potassium channel openers and other regulators of KATP channels.

1. Interest in ATP-sensitive K (KATP) channels first arose when it was shown that hypoglycaemic sulphonylureas, such as glibenclamide, closed these channels in pancreatic beta-cells to cause insulin release. The demonstration that certain smooth muscle relaxants (K channel openers) may exert their actions through opening a similar channel in vascular smooth muscle fueled further investigation of these channels and their physiological role in a variety of tissue types, including various types of smooth muscle, cardiac and skeletal muscle and neural and endocrine organ function. 2. The K channel openers have a variety of potential therapeutic applications, including disorders of smooth muscle 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 detail. One of the current problems is the lack of selectivity of KATP channel regulators. However, there have been a number of recent encouraging reports suggesting that, under certain pathophysiological conditions, the action of the K channel openers may be enhanced, conferring upon them some degree of selectivity. 3. A number of endogenous regulators of these channels have been identified, particularly in the category of endogenous openers of these channels. At present though, the physiological role of these channels and the endogenous regulators identified, is unclear. 4. It is evident that, although advances have been made, much work is still required to increase our understanding and ultimately to allow selective pharmacological manipulation of these channels to become a therapeutic reality.