Vascular Smooth Muscle Adenosine Triphosphate (ATP)-Sensitive Potassium Channel and Anesthetics

Abstract

Adenosine triphosphate-sensitive potassium channel (KATP channel) closed by intracellular adenosine triphosphate (ATP) appears widely distributed in the vascular system. Activation of vascular smooth muscle KATP channel with hyperpolarizing agents such as lemakalim results in membrane hyperpolarization, a consequent reduction in calcium influx through voltage-dependent calcium channel, and leads to vessel relaxation. In contrast to channel activation in vascular smooth muscle cell, channel-induced hyperpolarization of endothelial cells results in an increase in calcium influx, which could stimulate the production of nitric oxide and prostacyclin from the endothelial cell. channels response to change in the cellular metabolic status like ischemia and hypoxia, and are the target of a variety of synthetic and endogenous vasoactive substance. channel openers are used as therapeutic agent for cardiovascular disease. Endogenous channel-induced vasodilation is functionally important because it has been shown to modulate the pulmonary vasoconstrictor response to hypoxia and systemic hypotension in the pulmonary circulation, enhance tissue perfusion in response to hypoxia and severe hypotension in the systemic circulation. In virtro, halothane and intravenous anesthetics attenuated channel agonist, lemaklim-induced vasodilation. The coronary vasodilation by volatile anesthetics such as isoflurane, enflurane and halothane was associated with activation of channel in coronary artery. Further investigation is required to determine signal transduction pathway in detail stimulated by channel agonist in human blood vessel and effect of anesthetics on the channel-induced signal transduction, and role of channel of pathophysiology of vascular disease such as hypertension, angina.