Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Hiroki ToyodaEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101910


Historical Background

Based on the structural features, K + channels are classified into the voltage-gated K + channels, Ca 2+-dependent K + channels, and leak K + (two-pore-domain K +) channels (Fig. 1). The voltage-gated K + channels and Ca 2+-dependent K + channels form tetramers, with each subunit containing six or seven transmembrane domains and one pore domain while leak K + (two-pore-domain K +) channels form dimers, with each subunit containing four transmembrane domains and two pore domains (Goldstein et al. 2001; Bayliss et al. 2003). In excitable cells, a negative membrane potential is critical for electrical signaling, and it has long been considered that this key mechanism is largely mediated by leak K + currents (Goldman 1943). However, the molecular basis for...
This is a preview of subscription content, log in to check access.


  1. Bayliss DA, Barrett PQ. Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact. Trends Pharmacol Sci. 2008;29:566–75.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bayliss DA, Sirois JE, Talley EM. The TASK family: two-pore domain background K+ channels. Mol Interv. 2003;3:205–19.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Berg AP, Talley EM, Manger JP, Bayliss DA. Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. J Neurosci. 2004;24:6693–702.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Brickley SG, Aller MI, Sandu C, Veale EL, Alder FG, Sambi H, et al. TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons. J Neurosci. 2007;27:9329–40.  https://doi.org/10.1523/JNEUROSCI.1427-07.2007.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chen X, Talley EM, Patel N, Gomis A, McIntire WE, Dong B, et al. Inhibition of a background potassium channel by Gq protein α-subunits. Proc Natl Acad Sci USA. 2006;103:3422–7.  https://doi.org/10.1073/pnas.0507710103.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Choi Y, Yoon YW, Na HS, Kim SH, Chung JM. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain. 1994;59:369–76.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Clarke CE, Veale EL, Wyse K, Vandenberg JI, Mathie A. The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function. J Biol Chem. 2008;283:16985–92.  https://doi.org/10.1074/jbc.M801368200.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Czirjak G, Enyedi P. Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits. J Biol Chem. 2002;277:5426–32.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Czirjak G, Fischer T, Spat A, Lesage F, Enyedi P. TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II. Mol Endocrinol. 2000;14:863–74.  https://doi.org/10.1210/mend.14.6.0466.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dobler T, Springauf A, Tovornik S, Weber M, Schmitt A, Sedlmeier R, et al. TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones. J Physiol. 2007;585:867–79.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J. 1997;16:5464–71.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Enyedi P, Czirjak G. Molecular background of leak K+ currents: two-pore domain potassium channels. Physiol Rev. 2010;90:559–605.  https://doi.org/10.1152/physrev.00029.2009.CrossRefGoogle Scholar
  13. Fong GC, Shah PU, Gee MN, Serratosa JM, Castroviejo IP, Khan S, et al. Childhood absence epilepsy with tonic-clonic seizures and electroencephalogram 3-4-Hz spike and multispike-slow wave complexes: linkage to chromosome 8q24. Am J Hum Genet. 1998;63:1117–29.  https://doi.org/10.1086/302066.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Goldman DE. Potential, impedance, and rectification in membranes. J Gen Physiol. 1943;27:37–60.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Goldstein SA, Bockenhauer D, O’Kelly I, Zilberberg N. Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci. 2001;2:175–84.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Holter J, Carter D, Leresche N, Crunelli V, Vincent P. A TASK3 channel (KCNK9) mutation in a genetic model of absence epilepsy. J Mol Neurosci. 2005;25:37–51.  https://doi.org/10.1385/JMN:25:1:037.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Kananura C, Sander T, Rajan S, Preisig-Muller R, Grzeschik KH, Daut J, et al. Tandem pore domain K+-channel TASK-3 (KCNK9) and idiopathic absence epilepsies. Am J Med Genet. 2002;114:227–9.  https://doi.org/10.1002/ajmg.10201.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Kang D, Han J, Talley EM, Bayliss DA, Kim D. Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. J Physiol. 2004;554:64–77.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Karschin C, Wischmeyer E, Preisig-Muller R, Rajan S, Derst C, Grzeschik KH, et al. Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K+ channel subunit, TASK-5, associated with the central auditory nervous system. Mol Cell Neurosci. 2001;18:632–48.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Kim D, Gnatenco C. TASK-5, a new member of the tandem-pore K+ channel family. Biochem Biophys Res Commun. 2001;284:923–30.  https://doi.org/10.1006/bbrc.2001.5064.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kim Y, Bang H, Kim D. TBAK-1 and TASK-1, two-pore K+ channel subunits: kinetic properties and expression in rat heart. Am J Phys. 1999;277:H1669–78.Google Scholar
  22. Kim Y, Bang H, Kim D. TASK-3, a new member of the tandem pore K+ channel family. J Biol Chem. 2000;275:9340–7.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Kim DS, Kim JE, Kwak SE, Choi HC, Song HK, Kimg YI, et al. Up-regulated astroglial TWIK-related acid-sensitive K+ channel-1 (TASK-1) in the hippocampus of seizure-sensitive gerbils: a target of anti-epileptic drugs. Brain Res. 2007;1185:346–58.  https://doi.org/10.1016/j.brainres.2007.09.043.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Kim D, Cavanaugh EJ, Kim I, Carroll JL. Heteromeric TASK-1/TASK-3 is the major oxygen-sensitive background K+ channel in rat carotid body glomus cells. J Physiol. 2009;587:2963–75.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Koh JY, Suh SW, Gwag BJ, He YY, Hsu CY, Choi DW. The role of zinc in selective neuronal death after transient global cerebral ischemia. Science. 1996;272:1013–6.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Lauritzen I, Zanzouri M, Honore E, Duprat F, Ehrengruber MU, Lazdunski M, et al. K+-dependent cerebellar granule neuron apoptosis. Role of task leak K+ channels. J Biol Chem. 2003;278:32068–76.  https://doi.org/10.1074/jbc.M302631200.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Lazarenko RM, Willcox SC, Shu S, Berg AP, Jevtovic-Todorovic V, Talley EM, et al. Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics. J Neurosci. 2010;30:7691–704.  https://doi.org/10.1523/JNEUROSCI.1655-10.2010.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Lesage F. Pharmacology of neuronal background potassium channels. Neuropharmacol. 2003;44:1–7.CrossRefGoogle Scholar
  29. Linden AM, Aller MI, Leppa E, Vekovischeva O, Aitta-Aho T, Veale EL, et al. The in vivo contributions of TASK-1-containing channels to the actions of inhalation anesthetics, the α2 adrenergic sedative dexmedetomidine, and cannabinoid agonists. J Pharmacol Exp Ther. 2006;317:615–26.  https://doi.org/10.1124/jpet.105.098525.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Linden AM, Sandu C, Aller MI, Vekovischeva OY, Rosenberg PH, Wisden W, et al. TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation anesthetics. J Pharmacol Exp Ther. 2007;323:924–34.  https://doi.org/10.1124/jpet.107.129544.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Liu C, Cotten JF, Schuyler JA, Fahlman CS, Au JD, Bickler PE, et al. Protective effects of TASK-3 (KCNK9) and related 2P K channels during cellular stress. Brain Res. 2005;1031:164–73.  https://doi.org/10.1016/j.brainres.2004.10.029.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Lopes CM, Rohacs T, Czirjak G, Balla T, Enyedi P, Logothetis DE. PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels. J Physiol. 2005;564:117–29.  https://doi.org/10.1113/jphysiol.2004.081935.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Marsh B, Acosta C, Djouhri L, Lawson SN. Leak K+ channel mRNAs in dorsal root ganglia: relation to inflammation and spontaneous pain behaviour. Mol Cell Neurosci. 2012;49:375–86.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Meuth SG, Kleinschnitz C, Broicher T, Austinat M, Braeuninger S, Bittner S, et al. The neuroprotective impact of the leak potassium channel TASK1 on stroke development in mice. Neurobiol Dis. 2009;33:1–11.  https://doi.org/10.1016/j.nbd.2008.09.006.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Millar JA, Barratt L, Southan AP, Page KM, Fyffe RE, Robertson B, et al. A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proc Natl Acad Sci USA. 2000;97:3614–8.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Morenilla-Palao C, Luis E, Fernandez-Pena C, Quintero E, Weaver JL, Bayliss DA, et al. Ion channel profile of TRPM8 cold receptors reveals a role of TASK-3 potassium channels in thermosensation. Cell Rep. 2014;8:1571–82.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Muhammad S, Aller MI, Maser-Gluth C, Schwaninger M, Wisden W. Expression of the kcnk3 potassium channel gene lessens the injury from cerebral ischemia, most likely by a general influence on blood pressure. Neuroscience. 2010;167:758–64.  https://doi.org/10.1016/j.neuroscience.2010.02.024.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Mutch WA, Hansen AJ. Extracellular pH changes during spreading depression and cerebral ischemia: mechanisms of brain pH regulation. J Cereb Blood Flow Metab. 1984;4:17–27.  https://doi.org/10.1038/jcbfm.1984.3.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Rajan S, Wischmeyer E, Xin Liu G, Preisig-Muller R, Daut J, Karschin A, et al. TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor. J Biol Chem. 2000;275:16650–7.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, et al. Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J Biol Chem. 1998;273:30863–9.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Talley EM, Solorzano G, Lei Q, Kim D, Bayliss DA. CNS distribution of members of the two-pore-domain (KCNK) potassium channel family. J Neurosci. 2001;21:7491–505.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Tsodyks M. Spike-timing-dependent synaptic plasticity – the long road towards understanding neuronal mechanisms of learning and memory. Trends Neurosci. 2002;25:599–600.  https://doi.org/10.1016/S0166-2236(02)02294-4.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Wasterlain CG, Fujikawa DG, Penix L, Sankar R. Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia. 1993;34(Suppl 1):S37–53.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Wilke BU, Lindner M, Greifenberg L, Albus A, Kronimus Y, Bunemann M, et al. Diacylglycerol mediates regulation of TASK potassium channels by Gq-coupled receptors. Nat Commun. 2014;5:5540.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Xiong ZQ, Stringer JL. Extracellular pH responses in CA1 and the dentate gyrus during electrical stimulation, seizure discharges, and spreading depression. J Neurophysiol. 2000;83:3519–24.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Neuroscience and Oral PhysiologyOsaka University Graduate School of DentistrySuitaJapan