Is there a therapeutic future for 'potassium channel openers'?

1. Potassium channels, which control cell electrical activity, are among the most regulated of all ion channels in biology, Promotion of activity in K+ channels by a wide range of physiological factors tends to stabilize cell function, 2. The discovery of synthetic molecules (e.g, cromakalim) that 'directly' open ATP-sensitive K+ channels has led to a new direction in pharmacology. ATP-sensitive Kf channel-opening properties have subsequently been demonstrated in a diverse range of chemical structures (synthetic and endogenous), 3. The existence of so many different subtypes of K+ channels has been an impetus in the search of new potassium channel openers with different channel selectivities and thus biological profiles. 4. The decrease in cell excitability following Kf channel opening implies a broad clinical potential in a number of pathological conditions for K+ channel openers, Preclinical and clinical evidence supports therapeutic roles of K+ channel openers in disorders of a wide range of biological cells, 5. Although lack of selectivity of current compounds remains a major hurdle, advances in Kf channel openers and K+ channel pharmacology are encouraging, Differences already observed in the pharmacology of K+ channel openers are important factors for the development of second-generation compounds, when tissue selectivity is sought. 6. The availability of subtype-selective K+ channel openers will facilitate detailed study, through a combined effort of electrophysiology, functional pharmacology and molecular biology, leading to focused therapeutic approaches for defined pathological conditions.