Targeting TASK-1 channels as a therapeutic approach

Abstract

The voltage-independent background two-pore domain K+ channel TASK-1 sets the resting membrane potential in excitable cells and renders these cells sensitive to a variety of vasoactive factors. There is clear evidence for TASK-1 in human pulmonary artery smooth muscle cells and TASK-1 channels are likely to regulate the pulmonary vascular tone through their regulation by hypoxia, pH, inhaled anesthetics, and G protein-coupled pathways. Furthermore, TASK-1 is a strong candidate to play a role in hypoxic pulmonary vasoconstriction. On the other hand, consistent with the activation of TASK-1 channels by volatile anesthetics, TASK-1 contributes to the anesthetic-induced pulmonary vasodilation. TASK-1 channels are unique among K+ channels because they are regulated by both, increases and decreases from physiological pH, thus contributing to their protective effect on the pulmonary arteries. Moreover, TASK-1 may also have a critical role in mediating the vasoactive response of G protein-coupled pathways in resistance arteries which can offer promising therapeutic solutions to target diseases of the pulmonary circulation. © Humana Press, a part of Springer Science+ Business Media, LLC 2010.