Cloning and Expression of a Novel pH-sensitive Two Pore Domain K+Channel from Human Kidney

摘要: Abstract A complementary DNA encoding a novel K+ channel, called TASK-2, was isolated from human kidney and its gene mapped to chromosome 6p21. TASK-2 has low sequence similarity other two pore domain channels, such as TWIK-1, TREK-1, TASK-1, TRAAK (18–22% of amino acid identity), but similar topology consisting four potential membrane-spanning domains. In transfected cells, produces noninactivating, outwardly rectifying currents with activation thresholds that closely follow the K+equilibrium potential. As for related TASK-1 outward rectification is lost at high external K+concentration. The conductance estimated be 14.5 picosiemens in physiological conditions 59.9 symmetrical 155 mm K+. are blocked by quinine (IC50 = 22 μm) quinidine (65% inhibition 100 not classical channel blockers tetraethylammonium, 4-aminopyridine, Cs+. They only slightly sensitive Ba2+, less than 17% 1 mm. highly pH range. 10% maximum current recorded 6.5 90% 8.8. Unlike all cloned channels pore-forming domains, essentially absent brain. mouse, mainly expressed kidney, where situ hybridization shows it localized cortical distal tubules collecting ducts. This localization, well functional properties, suggest could play an important role renal transport.