Targeting TASK-1 channels as a therapeutic approach.
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.
Olschewski
Andrea
A
University Clinic of Anesthesia and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 29, A-8036, Graz, Austria. andrea.olschewski@meduni-graz.at
D018685:Anesthetics, Inhalation / Q000378:metabolism; D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
D018685:Anesthetics, Inhalation; D019332:Endothelin-1; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; C420132:potassium channel subfamily K member 3