Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney.
A complementary DNA encoding a novel K+ channel, called TASK-2, was isolated from human kidney and its gene was mapped to chromosome 6p21. TASK-2 has a low sequence similarity to other two pore domain K+ channels, such as TWIK-1, TREK-1, TASK-1, and TRAAK (18-22% of amino acid identity), but a similar topology consisting of four potential membrane-spanning domains. In transfected cells, TASK-2 produces noninactivating, outwardly rectifying K+ currents with activation potential thresholds that closely follow the K+ equilibrium potential. As for the related 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 physiological conditions and 59.9 picosiemens in symmetrical conditions with 155 mM K+. TASK-2 currents are blocked by quinine (IC50 = 22 microM) and quinidine (65% of inhibition at 100 microM) but not by the other classical K+ channel blockers tetraethylammonium, 4-aminopyridine, and Cs+. They are only slightly sensitive to Ba2+, with less than 17% of inhibition at 1 mM. As TASK-1, TASK-2 is highly sensitive to external pH in the physiological range. 10% of the maximum current was recorded at pH 6. 5 and 90% at pH 8.8. Unlike all other cloned channels with two pore-forming domains, TASK-2 is essentially 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.
Reyes
R
R
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Duprat
F
F
Lesage
F
F
Fink
M
M
Salinas
M
M
Farman
N
N
Lazdunski
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003001:Cloning, Molecular; D004553:Electric Conductivity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D015221:Potassium Channels / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain; D011487:Protein Conformation; D012333:RNA, Messenger / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
C109137:KCNK1 protein, human; C486372:Kcnk1 protein, mouse; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; D011994:Recombinant Proteins; C103742:potassium channel protein TREK-1; C420132:potassium channel subfamily K member 3