Therapeutic Potential of Potassium Channel Activators in Coronary Heart Disease

Potassium channel activators have the ability to open potassium channels in a variety of cells Since most of their effects are antagonized by antidiabetic sulfonylureas, the ATP-sensitive potassium channel is their likely target. Opening of potassium channels leads to hyperpolarization of the surface membrane with consequent closure of voltage-dependent ion channels and reduction of free intracellular calcium ions. Currently available potassium channel activators, including aprikalim, bimakalim, cromakalim, emakalim, nicorandil, pinacidil etc., display a high affinity for potassium channels of vascular smooth muscle. Vasodilation and a reduction in systemic vascular resistance are their prominent pharmacological effects. Coronary and cerebral arteries are highly sensitive to potassium channel activator-induced dilation. Apart from treatment of hypertension, potassium channel activators appear to have therapeutic potential in coronary heart disease. They reduce cardiac afterload, increase native and collateral coronary blood flow and reduce the size of experimental myocardial infarcts. This last effect cannot be satisfactorily explained entirely by haemodynamic or coronary vascular actions of potasium channel activators and a cardioprotective effect is postulated. For these drugs ischaemia-induced and activatorinduced opening of cardiac ATP-sensitive potassium channels appear to work in concert. Nicorandil combines the pharmacological properties of an organic nitrate with those of potassium channel activators. Experimenta1 and clinical results characterize nicorandil as a unique and promising drug for the treatment of coronary heart disease.