CLONING AND EXPRESSION OF A NOVEL PH-SENSITIVE 2 PORE DOMAIN K+ CHANNEL FROM HUMAN KIDNEY

A complementary DNA encoding a novel K+ channel, called TASK-2, was is olated from human kidney and its gene was mapped to chromosome 6p21. T ASK-a has a low sequence similarity to other two pore domain Kf channe ls, such as TWIK-1, TREK-1, TASK-1, and TRAAK (18-22% of amino acid id entity), but a similar topology consisting of four potential membrane- spanning domains. In transfected cells, TASK-2 produces noninactivatin g, outwardly rectifying K+ currents with activation potential threshol ds that closely follow the K+ equilibrium potential, As for the relate d TASK-1 and TRAAK channels, the outward rectification is lost at high external K+ concentration. The conductance of TASK-2 was estimated to be 14.5 picosiemens in physio logical conditions and 59.9 picosiemens in symmetrical conditions with 155 mM K+. TASK-2 currents are blocked by quinine (IC50 = 22 mu M) and quinidine (65% of inhibition at 100 m u M) but not by the other classical K+ channel blockers tetraethylammo nium, 4-aminopyridine, and Cs+. They are only slightly sensitive to Ba 2+, with less than 17% of inhibition at 1 mM. As TASK-1, TASK-2 is hig hly sensitive to external pH in the physiological range. 10% of the ma ximum current was recorded at pH 6.5 and 90% at pH 8.8, Unlike all oth er cloned channels with two pore-forming domains, TASK-2 is essentiall y absent in the brain. In human and mouse, TASK-2 is mainly expressed in the kidney, where in situ hybridization shows that it is localized in cortical distal tubules and collecting ducts. This localization, as well as its functional properties, suggest that TASK-2 could play an important role in renal K+ transport.