Current trends in the study of potassium channel openers.
Some eight years ago it was found that certain smooth muscle relaxants exert their effect by opening a specific K+ channel resulting in cell membrane hyperpolarization. The use of K+ channel openers (cromakalim, pinacidil and RP-52891) and compounds which antagonize their actions (glibenclamide, phentolamine and alinidine) has enabled a great deal of research to be performed into the role of this K+ channel, not only in smooth muscle, but also in cardiac and skeletal muscle as well as neural and endocrine organ function. Much of the attention has centred on the smooth muscle relaxant actions of the K+ channel openers, since they have potential therapeutic use in disorders involving smooth muscle over-reactivity such as hypertension and asthma. More recently the cardiac actions of the K+ channel openers have become the focus of interest. Although there appear to be good theoretical reasons why K+ channel openers may be of use in some arrhythmias and in ischaemic heart disease there are major hurdles to overcome. In particular, given that the effect of these compounds on vascular smooth muscle occurs at a concentration 20- to 100-fold lower than that required to produce cardiac effects, it is likely their therapeutic usefulness will be limited until a breakthrough in cardiac/vascular selectivity is made. There is also growing interest in endogenous K+ channel openers and the physiological role of the K+ channel which they open. Opening of K+ channels, either spontaneously or by endogenous regulators, could possibly be an important hypotensive mechanism both under normal conditions and in a number of pathological conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
McPherson
G A
GA
Baker Medical Research Institute, Prahran, Victoria, Australia.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D006197:Hair / Q000187:drug effects; D006801:Humans; D009132:Muscles / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D015221:Potassium Channels; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000255:Adenosine Triphosphate