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KCNK5  -  potassium channel, two pore domain...

Homo sapiens

Synonyms: Acid-sensitive potassium channel protein TASK-2, K2p5.1, Potassium channel subfamily K member 5, TASK-2, TASK2, ...
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Disease relevance of KCNK5


Psychiatry related information on KCNK5

  • When two tasks are presented within a short stimulus-onset-asynchrony (SOA), reaction time of each task, especially task 2, is dramatically delayed [6].
  • In task 2, control animals showed poor retention; beta-endorphin caused amnesia at the dose of 0.1 but not 1.0 microgram/kg; the other three drugs caused memory facilitation; naloxone potentiated the facilitatory effect of ACTH and epinephrine; and beta-endorphin reversed it and transformed it into a deep amnesia [7].
  • As a result of this difference, in the psychological refractory period paradigm, the central capacity sharing model predicts that lengthening Task 2 precentral processing will improve Task 1 performance at short stimulus onset asynchronies, whereas the central bottleneck model does not [8].
  • Conceptual understanding was assessed by the ability to spontaneously use such relational properties in problem solving (Task 1) and to recognize and explain them when prompted (Task 2) [9].

High impact information on KCNK5


Biological context of KCNK5


Anatomical context of KCNK5

  • RESULTS: Expression of KCNK5 was detected in cerebral cortex, medulla, and spinal cord [13].
  • When heterologously expressed in Xenopus oocytes, KCNK5 currents exhibited delayed activation, outward rectification, proton sensitivity, and modulation by protein kinase C. Clinical concentrations of volatile general anesthetics potentiated KCNK5 currents by 8-30% [13].
  • Astrocytes situated in rat cerebellar tissue sections were positive for TASK-2 channels [16].
  • TASK2 also showed intracellular localization in mononucleate cytotrophoblast cells in culture and expression was lost with multinucleation [17].
  • During task 2 performance, SPMS patients had more significant activations of the contralateral primary sensorimotor cortex and thalamus and of the ipsilateral upper bank of sylvian fessure [18].

Associations of KCNK5 with chemical compounds

  • It is concluded that the proposed disulphide bond between cysteine 51 residues of KCNK5 subunits does occur and preserves a dimeric structure in the detergent solubilized complex [19].
  • Lidocaine (1 mM) inhibited TASK-2 currents by 55 +/- 4%, whereas its quaternary positively charged analog N-ethyl lidocaine (QX314) had no effect [15].
  • Additionally, we found that TASK-2 single channel activity, like the Type 4 conductance is potentiated by cytoplasmic arachidonic acid (20 microM) and inhibited by cytoplasmic TEA (1 mM) [20].
  • TASK-2 does not possess a histidine residue at the homologous position [21].
  • Neither hTBAK1 nor hTASK2 was activated following stimulations with LTD4 (0.1 and 100 nM) [22].

Physical interactions of KCNK5

  • The present set of experiments investigated the Bereitschaftspotential (BP) preceding voluntary bimanual sequential simple (task 1) and complex movements (task 2) in supplementary/cingulate and primary motor areas (SCMA, MIs) using 64-channel direct current electroencephalography analysis in 16 right-handed healthy subjects [23].

Regulatory relationships of KCNK5

  • Contrary to this conception, the authors found backward response-level crosstalk effects in which Task 2 response force requirements influenced the force-time dynamics of Task 1 responses [24].

Other interactions of KCNK5

  • In this work, the distributions of some acid-sensitive two-pore-domain K+ channels (TASK-1, TASK-2 and TASK-3) were investigated in the rat and human cerebellum [16].
  • Zinc was found to be a selective blocker of TASK-3 with virtually no effect on TASK-1 or TASK-2 [25].
  • RT-PCR indicated expression of the Ca2+-activated K+ channel KCNN4, as well as the acid-sensitive, four transmembrane domain, two pore K+ channel, KCNK5 (hTASK-2) [26].
  • The first two subunits, TALK-1 and TALK-2, are distantly related to TASK-2 [27].
  • RESULT(S): Molecular analysis demonstrated expression and specific regional distribution of TRAAK, TREK-1, and TASK-2 in nonhuman primate sperm [28].

Analytical, diagnostic and therapeutic context of KCNK5

  • CONCLUSION: Human KCNK5 is a tandem pore domain potassium channel exhibiting delayed activation and sensitivity to volatile anesthetics and may therefore have a role in suppressing cellular excitability during general anesthesia [13].
  • 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 [14].
  • Immunofluorescence showed that TASK2 had an intracellular localization within the trophoblast of first trimester villi but was less abundant and restricted to stem villi at term [17].
  • Western blot analysis verified the expression of CLC channels, as well as KCNK5 [26].
  • We scan 12 subjects using functional MRI while they conduct two tasks-shape discrimination in task 1 and color discrimination in task 2-and vary the SOA between tasks as 100 or 1500 ms [6].


  1. Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Medhurst, A.D., Rennie, G., Chapman, C.G., Meadows, H., Duckworth, M.D., Kelsell, R.E., Gloger, I.I., Pangalos, M.N. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  2. Tinnitus and its effect on working memory and attention. Rossiter, S., Stevens, C., Walker, G. J. Speech Lang. Hear. Res. (2006) [Pubmed]
  3. The psychological refractory period in Parkinson's disease. Hsieh, S. Perceptual and motor skills. (2000) [Pubmed]
  4. Fifteen-count breathlessness score in adults with COPD. Williams, M., De Palma, L., Cafarella, P., Petkov, J. Respirology (2006) [Pubmed]
  5. Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. Warth, R., Barrière, H., Meneton, P., Bloch, M., Thomas, J., Tauc, M., Heitzmann, D., Romeo, E., Verrey, F., Mengual, R., Guy, N., Bendahhou, S., Lesage, F., Poujeol, P., Barhanin, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. Resolving dual-task interference: an fMRI study. Jiang, Y. Neuroimage (2004) [Pubmed]
  7. Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphin with ACTH or epinephrine on memory consolidation. Izquierdo, I., Dias, R.D. Psychoneuroendocrinology (1983) [Pubmed]
  8. Testing the predictions of the central capacity sharing model. Tombu, M., Jolicoeur, P. Journal of experimental psychology. Human perception and performance. (2005) [Pubmed]
  9. The role of conceptual understanding in children's addition problem solving. Canobi, K.H., Reeve, R.A., Pattison, P.E. Developmental psychology. (1998) [Pubmed]
  10. Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel. Niemeyer, M.I., Gonz??lez-Nilo, F.D., Z????iga, L., Gonz??lez, W., Cid, L.P., Sep??lveda, F.V. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  11. pH sensing in the two-pore domain K+ channel, TASK2. Morton, M.J., Abohamed, A., Sivaprasadarao, A., Hunter, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. Niemeyer, M.I., Cid, L.P., Barros, L.F., Sepúlveda, F.V. J. Biol. Chem. (2001) [Pubmed]
  13. Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5. Gray, A.T., Zhao, B.B., Kindler, C.H., Winegar, B.D., Mazurek, M.J., Xu, J., Chavez, R.A., Forsayeth, J.R., Yost, C.S. Anesthesiology (2000) [Pubmed]
  14. Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. Reyes, R., Duprat, F., Lesage, F., Fink, M., Salinas, M., Farman, N., Lazdunski, M. J. Biol. Chem. (1998) [Pubmed]
  15. Amide local anesthetics potently inhibit the human tandem pore domain background K+ channel TASK-2 (KCNK5). Kindler, C.H., Paul, M., Zou, H., Liu, C., Winegar, B.D., Gray, A.T., Yost, C.S. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  16. Differential distribution of TASK-1, TASK-2 and TASK-3 immunoreactivities in the rat and human cerebellum. Rusznák, Z., Pocsai, K., Kovács, I., Pór, A., Pál, B., Bíró, T., Szücs, G. Cell. Mol. Life Sci. (2004) [Pubmed]
  17. TASK channel expression in human placenta and cytotrophoblast cells. Bai, X., Lacey, H.A., Greenwood, S.L., Baker, P.N., Turner, M.A., Sibley, C.P., Fyfe, G.K. J. Soc. Gynecol. Investig. (2006) [Pubmed]
  18. A functional magnetic resonance imaging study of patients with secondary progressive multiple sclerosis. Rocca, M.A., Gavazzi, C., Mezzapesa, D.M., Falini, A., Colombo, B., Mascalchi, M., Scotti, G., Comi, G., Filippi, M. Neuroimage (2003) [Pubmed]
  19. Extracellular conserved cysteine forms an intersubunit disulphide bridge in the KCNK5 (TASK-2) K+ channel without having an essential effect upon activity. Niemeyer, M.I., Cid, L.P., Valenzuela, X., Paeile, V., Sepúlveda, F.V. Mol. Membr. Biol. (2003) [Pubmed]
  20. Identification of native rat cerebellar granule cell currents due to background K channel KCNK5 (TASK-2). Cotten, J.F., Zou, H.L., Liu, C., Au, J.D., Yost, C.S. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  21. Determinants of pH sensing in the two-pore domain K(+) channels TASK-1 and -2. Morton, M.J., O'Connell, A.D., Sivaprasadarao, A., Hunter, M. Pflugers Arch. (2003) [Pubmed]
  22. Co-expression of mCysLT1 receptors and IK channels in Xenopus laevis oocytes elicits LTD4-stimulated IK current, independent of an increase in [Ca2+]i. Wulff, T., Hougaard, C., Klaerke, D.A., Hoffmann, E.K. Biochim. Biophys. Acta (2004) [Pubmed]
  23. High resolution DC-EEG mapping of the Bereitschaftspotential preceding simple or complex bimanual sequential finger movement. Cui, R.Q., Huter, D., Egkher, A., Lang, W., Lindinger, G., Deecke, L. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2000) [Pubmed]
  24. Backward response-level crosstalk in the psychological refractory period paradigm. Miller, J., Alderton, M. Journal of experimental psychology. Human perception and performance. (2006) [Pubmed]
  25. Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc. Clarke, C.E., Veale, E.L., Green, P.J., Meadows, H.J., Mathie, A. J. Physiol. (Lond.) (2004) [Pubmed]
  26. Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF. Fong, P., Argent, B.E., Guggino, W.B., Gray, M.A. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  27. Genomic and functional characteristics of novel human pancreatic 2P domain K(+) channels. Girard, C., Duprat, F., Terrenoire, C., Tinel, N., Fosset, M., Romey, G., Lazdunski, M., Lesage, F. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  28. Expression of two-pore domain potassium channels in nonhuman primate sperm. Chow, G.E., Muller, C.H., Curnow, E.C., Hayes, E.S. Fertil. Steril. (2007) [Pubmed]
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