Potassium Channel Activation in Vascular Smooth Muscle

Abstract

K+ channel opening causing membrane hyperpolarization in vascular smooth muscle and thereby vasodilatation, cannot be rated as the ‘newly discovered’ action principle of certain pharmacological substances but as an ubiquitous physiological mechanism for the relaxation in smooth muscle. Acidification of the serum-pH-value is such an effector influence initiating vasodilatation. Drugs such as pinacidil, nicorandil, minoxidil sulphate and cromakalim effect vasodilatation by membrane hyperpolarization of the vascular smooth muscle cells as well, which in some tissues raises the membrane potential to a value close to the K⁺ equilibrium potential [36]. Although the number of K⁺ channels observed is steadily but rapidly increasing, they can still be classified. They are usually subdivided according to their mode of activation. Some are activated strictly voltage-dependently, others by a variation in the intracellular Ca²⁺ concentration, and some by the internal concentration of ATP, Na⁺, cyclic nucleotides etc. The heterogeneous group of K⁺ channel openers may be a potential therapy for hypertension, asthma, peripheral vascular disease, and diseases of the heart and nervous system. The central starting point of their physiological mode of action is the hyperpolarization of the smooth muscle cells which leads to relaxation by closing T- and/or L-type Ca²⁺ channels without, in the classical sense, the participation of cAMP or cGMP [34]. We would like to discuss this problem from a physiological point of view and venture a wider definition of the term ’K⁺ channel opener’. This seems to be justified by the fact that cyclic nucleotides also elicit a membrane hyperpolarization in the vascular smooth muscle.