POTASSIUM CHANNEL OPENERS AND OTHER REGULATORS OF K_ATP CHANNELS

Abstract

SUMMARY1. Interest in ATP-sensitive K (KATP) channels first arose when it was shown that hypoglycaemic sulphonylureas, such as glibenclamide, closed these channels in pancreatic p-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 fuelled 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.

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

“…Noma discovered ATP-sensitive K + channels in cardiac myocytes (1097), and currents through similar channels were subsequently identified in many other cell types including vascular SMCs [see (9, 15, 68–72, 76, 166, 180, 219, 272, 273, 311, 322, 374, 375, 436, 506, 544, 661, 786, 826, 827, 984, 1070, 1111, 1182, 1183, 1187, 1188, 1332, 1464, 1595, 1604) for reviews]. These K + channels derive their name from their property that increases in intracellular ATP decrease their activity.…”

Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: A pilot, double‐blind, randomized, placebo‐controlled trial

“…Topical administration of minoxidil has been shown to be effective in treating AGA in men by thickening hair shafts, 4 and for FPHL by increasing hair weight and number 5 . Minoxidil induces hair growth by increasing the proliferation of follicular epithelial cells via the stimulation of blood microcapillary circulation by opening potassium channels 6 . It was proposed that an adenosine‐mediated signal transduction pathway contributes to hair growth based on evidence that the activation of adenosine receptors regulates minoxidil‐induced production of vascular endothelial growth factor (VEGF) in cultured dermal papilla cells 7 .…”

Pharmacology of the K‐ATP Channel Blocking Morpholinoguanidine PNU‐37883A

“…The last two decades have seen enormous growth in our understanding of ion channel structure and function. In particular, adenosine-5'-triphosphate-sensitive potassium (K-ATP) channels have been intensely investigated because of their wide distribution, key role in linking cellular metabolism to membrane potential, and therapeutic potential of K-ATP modulators (4,14,36,95). Many other reports have further described how K-ATP channels help to control insulin secretion (3,24,96), vascular smooth muscle tone (31,94,109), myocardial contractility and preconditioning (5,32,37,64), and renal tubular function (46,93,104,118).…”