Functional roles of KATP channels in vascular smooth muscle

1. ATP-sensitive potassium channels (K(ATP)) are present in vascular smooth muscle cells and play important roles in the vascular responses to a variety of pharmacological and endogenous vasodilators. 2. The K(ATP) channels are composed of four inwardly rectifying K+ channel subunits and four regulatory sulphonylurea receptors. The K(ATP) channels are inhibited by intracellular ATP and by sulphonylurea agents. 3. Pharmacological vasodilators such as cromakalim, pinacidil and diazoxide directly activate K(ATP) channels. The associated membrane hyperpolarization closes voltage-dependent Ca2+ channels, which leads to a reduction in intracellular Ca2+ and vasodilation. 4. Endogenous vasodilators such as calcitonin gene-related peptide, vasoactive intestinal polypeptide, prostacylin and adenosine activate K(ATP) by stimulating the formation of cAMP and increasing the activity of protein kinase A. Part of the mechanism of contraction of endogenous vasoconstrictors is due to inhibition of K(ATP) channels. 5. The K(ATP) channels appear to be tonically active in some vascular beds and contribute to the physiological regulation of vascular tone and blood flow. These channels also are activated under pathophysiological conditions, such as hypoxia, ischaemia, acidosis and septic shock, and, in these disease states, may play an important role in the regulation of tissue perfusion.