tandem pore domain potassium channels


Summary: Potassium channels that contain two pores in tandem. They are responsible for baseline or leak currents and may be the most numerous of all K channels.

Top Publications

  1. Hajdu P, Ulens C, Panyi G, Tytgat J. Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K+ channel. Cardiovasc Res. 2003;58:46-54 pubmed
    ..Our mutagenesis study revealed that NORP interacts with the selectivity filter of cTBAK-1. The significant role of the GYGD motif in this type of K(+) channels is emphasized. ..
  2. Alloui A, Zimmermann K, Mamet J, Duprat F, Noel J, Chemin J, et al. TREK-1, a K+ channel involved in polymodal pain perception. EMBO J. 2006;25:2368-76 pubmed
    ..TREK-1 appears as an important ion channel for polymodal pain perception and as an attractive target for the development of new analgesics. ..
  3. Kelly D, Mackenzie L, Hunter P, Smaill B, Saint D. Gene expression of stretch-activated channels and mechanoelectric feedback in the heart. Clin Exp Pharmacol Physiol. 2006;33:642-8 pubmed
    ..5. The importance of MEF and the non-homogeneous gene expression and strain distribution for arrhythmias is discussed. ..
  4. Bai X, Bugg G, Greenwood S, Glazier J, Sibley C, Baker P, et al. Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium. Reproduction. 2005;129:525-30 pubmed
    ..Therefore, we conclude that the human myometrium is a site of expression for the two-pore domain K+ channel proteins TASK1 and TREK1. ..
  5. Enyeart J, Xu L, Danthi S, Enyeart J. An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1. J Biol Chem. 2002;277:49186-99 pubmed
    ..The activation of I(AC) by ATP indicates that native bTREK-1 channels may function as sensors that couple the metabolic state of the cell to membrane potential, perhaps through an associated ATP-binding protein. ..
  6. Maingret F, Honore E, Lazdunski M, Patel A. Molecular basis of the voltage-dependent gating of TREK-1, a mechano-sensitive K(+) channel. Biochem Biophys Res Commun. 2002;292:339-46 pubmed
    ..Preferential opening of TREK-1 at depolarized potentials will greatly affect action potential duration, recovery from inactivation and neuronal repetitive firing activity. ..
  7. Kim D, Fujita A, Horio Y, Kurachi Y. Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Circ Res. 1998;82:513-8 pubmed
    ..Thus, the current flowing through the channel may contribute to the cardiac cellular electrical activity as a linear background K+ conductance. Therefore, we designated the clone cTBAK (cardiac two-pore background K+ channel). ..
  8. Veale E, Buswell R, Clarke C, Mathie A. Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide. Br J Pharmacol. 2007;152:778-86 pubmed
    ..Physiologically, methanandamide block of TASK1 and TASK3 channels may underpin a number of CNS effects of cannabinoids that are not mediated through activation of CB1 or CB2 receptors. ..
  9. Ben Abu Y, Zhou Y, Zilberberg N, Yifrach O. Inverse coupling in leak and voltage-activated K+ channel gates underlies distinct roles in electrical signaling. Nat Struct Mol Biol. 2009;16:71-9 pubmed publisher

More Information


  1. Aller M, Veale E, Linden A, Sandu C, Schwaninger M, Evans L, et al. Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons. J Neurosci. 2005;25:11455-67 pubmed
    ..However, TASK channel subunit composition does not alter the resting excitability of CGNs but does influence sensitivity to endogenous modulators such as Zn2+ and H+. ..
  2. Franks N, Honore E. The TREK K2P channels and their role in general anaesthesia and neuroprotection. Trends Pharmacol Sci. 2004;25:601-8 pubmed
  3. Clarke C, Veale E, Green P, Meadows H, Mathie A. Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc. J Physiol. 2004;560:51-62 pubmed
    ..Therefore it is possible that inhibition of IK(SO) in cerebellar granule cells by synaptically released zinc may have important physiological consequences. ..
  4. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, et al. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 1996;15:6854-62 pubmed
    ..They also show that different members in this structural family can have totally different functional properties. ..
  5. Yuill K, Ashmole I, Stanfield P. The selectivity filter of the tandem pore potassium channel TASK-1 and its pH-sensitivity and ionic selectivity. Pflugers Arch. 2004;448:63-9 pubmed
    ..39+/-0.03 (n=14) in H98D, 0.64+/-0.04 (n=18) in D204H and 0.33+/-0.07 (n=3) in D204N. Thus, the arrangement of ring of residues HDHD appears to optimise both pH sensitivity and ionic selectivity. ..
  6. Yuill K, Stansfeld P, Ashmole I, Sutcliffe M, Stanfield P. The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1: contributions of the pore domains. Pflugers Arch. 2007;455:333-48 pubmed
    ..Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter. ..
  7. Koh S, Monaghan K, Sergeant G, Ro S, Walker R, Sanders K, et al. TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. An essential role in smooth muscle inhibitory neurotransmission. J Biol Chem. 2001;276:44338-46 pubmed
    ..TREK-1 encodes a component of the stretch-activated K(+) conductance in smooth muscles and may contribute to nitrergic inhibition of gastrointestinal muscles. ..
  8. Niemeyer M, Cid L, Barros L, Sepulveda F. Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. J Biol Chem. 2001;276:43166-74 pubmed
    ..The presence of mTASK-2 in Ehrlich cells, its functional similarities with I(K, vol), and its modulation by changes in cell volume suggest that this two-pore domain K(+) channel participates in the regulatory volume decrease phenomenon. ..
  9. Patel A, Honore E. Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci. 2001;24:339-46 pubmed
    ..The pharmacological modulation of this novel class of ion channels could be of interest for both general anaesthesia and ischaemic neuroprotection. ..
  10. Putzke C, Wemhöner K, Sachse F, Rinné S, Schlichthörl G, Li X, et al. The acid-sensitive potassium channel TASK-1 in rat cardiac muscle. Cardiovasc Res. 2007;75:59-68 pubmed
    ..Our results suggest that in rat cardiomyocytes I(TASK) makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via alpha1A-adrenergic receptors. ..
  11. Thümmler S, Duprat F, Lazdunski M. Antipsychotics inhibit TREK but not TRAAK channels. Biochem Biophys Res Commun. 2007;354:284-9 pubmed
    ..Furthermore, TREK channels could play a role in the pathophysiology of psychiatric disorders such as depression and schizophrenia. ..
  12. Chemin J, Patel A, Duprat F, Zanzouri M, Lazdunski M, Honore E. Lysophosphatidic acid-operated K+ channels. J Biol Chem. 2005;280:4415-21 pubmed
    ..Gating conversion of the 2P domain K+ channels by intracellular LPA represents a novel form of ion channel regulation. Thus, the TREK and TRAAK channels should be included in the LPA-associated physiological and disease states. ..
  13. Maingret F, Patel A, Lazdunski M, Honore E. The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1. EMBO J. 2001;20:47-54 pubmed
    ..TASK-1 constitutes a novel sensitive molecular target for this endocannabinoid. ..
  14. 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 pubmed
    ..This localization, as well as its functional properties, suggest that TASK-2 could play an important role in renal K+ transport. ..
  15. Besana A, Barbuti A, Tateyama M, Symes A, Robinson R, Feinmark S. Activation of protein kinase C epsilon inhibits the two-pore domain K+ channel, TASK-1, inducing repolarization abnormalities in cardiac ventricular myocytes. J Biol Chem. 2004;279:33154-60 pubmed
    ..Furthermore, site-directed mutagenesis studies have identified threonine 381, in the C-terminal tail of murine TASK-1, as a critical residue in this regulation. ..
  16. Liu W, Saint D. Heterogeneous expression of tandem-pore K+ channel genes in adult and embryonic rat heart quantified by real-time polymerase chain reaction. Clin Exp Pharmacol Physiol. 2004;31:174-8 pubmed
    ..5. The physiological implications of the differential gene expression of the tandem-pore K+ channels is discussed. ..
  17. Hervieu G, Cluderay J, Gray C, Green P, Ranson J, Randall A, et al. Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS. Neuroscience. 2001;103:899-919 pubmed
    ..These studies indicate a widespread distribution of TREK-1 potassium channels throughout the rat brain and spinal cord, with expression in a number of areas being demonstrated to be present on GABA-containing neurones. ..
  18. Enyeart J, Danthi S, Liu H, Enyeart J. Angiotensin II inhibits bTREK-1 K+ channels in adrenocortical cells by separate Ca2+- and ATP hydrolysis-dependent mechanisms. J Biol Chem. 2005;280:30814-28 pubmed
    ..The novel Ca2+-dependent pathway is distinctive in its lack of ATP dependence, and is clearly different from the calmodulin kinase-dependent mechanism by which AngII modulates T-type Ca2+ channels in these cells. ..
  19. de la Cruz I, Levin J, Cummins C, Anderson P, Horvitz H. sup-9, sup-10, and unc-93 may encode components of a two-pore K+ channel that coordinates muscle contraction in Caenorhabditis elegans. J Neurosci. 2003;23:9133-45 pubmed
    ..elegans, Drosophila, and humans. Our results indicate that SUP-9 and perhaps other two-pore K+ channels function as multiprotein complexes, and that UNC-93 and SUP-10 likely define new classes of ion channel regulatory proteins. ..
  20. Xian Tao Li -, Dyachenko V, Zuzarte M, Putzke C, Preisig Müller R, Isenberg G, et al. The stretch-activated potassium channel TREK-1 in rat cardiac ventricular muscle. Cardiovasc Res. 2006;69:86-97 pubmed
  21. Han J, Truell J, Gnatenco C, Kim D. Characterization of four types of background potassium channels in rat cerebellar granule neurons. J Physiol. 2002;542:431-44 pubmed
    ..Our results also show that the high sensitivity of I(K,SO) to extracellular pH comes from the high sensitivity of Type 2 (TASK-3) and Type 4 K+ channels. ..
  22. Lopes C, Gallagher P, Buck M, Butler M, Goldstein S. Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J Biol Chem. 2000;275:16969-78 pubmed
    ..Single Kcnk3 channels open across the physiological voltage range; hence they are "leak" conductances; however, they open only briefly and rarely even after exposure to agents that activate other potassium channels. ..
  23. Talley E, Bayliss D. Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action. J Biol Chem. 2002;277:17733-42 pubmed
    ..Our results also indicate a close molecular relationship between these two forms of modulation, one endogenous and the other clinically applied. ..
  24. Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M, et al. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J. 2004;23:2684-95 pubmed
    ..Trek1-/- mice are also resistant to anesthesia by volatile anesthetics. TREK-1 emerges as a potential innovative target for developing new therapeutic agents for neurology and anesthesiology. ..
  25. Sandoz G, Thümmler S, Duprat F, Feliciangeli S, Vinh J, Escoubas P, et al. AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K(+) channels into open leak channels. EMBO J. 2006;25:5864-72 pubmed
    ..The association of AKAP150 with TREK channels integrates them into a postsynaptic scaffold where both G-protein-coupled membrane receptors (as demonstrated here for beta2AR) and TREK-1 dock simultaneously. ..
  26. Gordon J, Hen R. TREKing toward new antidepressants. Nat Neurosci. 2006;9:1081-3 pubmed
  27. Hughes S, Magnay J, Foreman M, Publicover S, Dobson J, El Haj A. Expression of the mechanosensitive 2PK+ channel TREK-1 in human osteoblasts. J Cell Physiol. 2006;206:738-48 pubmed
    ..We hypothesise a possible role for TREK-1 in mechanotransduction, leading to bone remodelling. ..
  28. Lauritzen I, Chemin J, Honore E, Jodar M, Guy N, Lazdunski M, et al. Cross-talk between the mechano-gated K2P channel TREK-1 and the actin cytoskeleton. EMBO Rep. 2005;6:642-8 pubmed
    ..Conversely, the actin cytoskeleton tonically represses TREK-1 mechano-sensitivity. Thus, the dialogue between TREK-1 and the actin cytoskeleton might influence both synaptogenesis and neuronal electrogenesis. ..
  29. Lesage F, Lazdunski M. Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol. 2000;279:F793-801 pubmed
  30. Maingret F, Lauritzen I, Patel A, Heurteaux C, Reyes R, Lesage F, et al. TREK-1 is a heat-activated background K(+) channel. EMBO J. 2000;19:2483-91 pubmed
    ..Expression of TREK-1 in peripheral sensory neurons as well as in central hypothalamic neurons makes this K(+) channel an ideal candidate as a physiological thermoreceptor. ..
  31. Meadows H, Benham C, Cairns W, Gloger I, Jennings C, Medhurst A, et al. Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel. Pflugers Arch. 2000;439:714-22 pubmed
    ..Only low levels of expression were seen in the majority of peripheral regions. Thus, hTREK-1, although functionally and pharmacologically similar to mouse TREK-1, appears to have a more CNS-specific distribution. ..
  32. Li Z, Zhang H, Li L, Wang X. Enhanced expressions of arachidonic acid-sensitive tandem-pore domain potassium channels in rat experimental acute cerebral ischemia. Biochem Biophys Res Commun. 2005;327:1163-9 pubmed
    ..These results suggested a strong correlation between TREK channels and acute cerebral ischemia. TREK channels might provide a neuroprotective mechanism in the pathological process. ..
  33. Andres Enguix I, Caley A, Yustos R, Schumacher M, Spanu P, Dickinson R, et al. Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: molecular cloning of an anesthetic-activated potassium channel from Lymnaea stagnalis. J Biol Chem. 2007;282:20977-90 pubmed
    ..The L159A mutation in LyTASK disrupts the stereoselective response to isoflurane while having no effect on the pH sensitivity of the channel, suggesting this critical amino acid may form part of an anesthetic binding site...
  34. Berg A, Talley E, Manger J, Bayliss D. 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 pubmed
  35. Bockenhauer D, Zilberberg N, Goldstein S. KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nat Neurosci. 2001;4:486-91 pubmed
    ..The findings reveal a pathway for dynamic regulation of excitability. ..
  36. Perlis R, Moorjani P, Fagerness J, Purcell S, Trivedi M, Fava M, et al. Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study. Neuropsychopharmacology. 2008;33:2810-9 pubmed publisher
    ..More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response. ..
  37. Niemeyer M, Cid L, Sepulveda F. K+ conductance activated during regulatory volume decrease. The channels in Ehrlich cells and their possible molecular counterpart. Comp Biochem Physiol A Mol Integr Physiol. 2001;130:565-75 pubmed
    ..Preliminary experiments show the presence of the TASK-2 channel, a member of the 2P-4TM family inhibited by acid extracellular pH, in Ehrlich cells and suggest that it might underlie the swelling-induced K+ current. ..
  38. Gu W, Schlichthörl G, Hirsch J, Engels H, Karschin C, Karschin A, et al. Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. J Physiol. 2002;539:657-68 pubmed
    ..Our results suggest that alternative splicing of TREK-2 contributes to the diversity of two-pore-domain K+ channels. ..
  39. Czirják G, Enyedi P. TASK-3 dominates the background potassium conductance in rat adrenal glomerulosa cells. Mol Endocrinol. 2002;16:621-9 pubmed
    ..The high level of expression and its pharmacological properties suggest that TASK-3 dominates the resting potassium conductance of glomerulosa cells. ..
  40. Washburn C, Sirois J, Talley E, Guyenet P, Bayliss D. Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance. J Neurosci. 2002;22:1256-65 pubmed
  41. Honore E. The neuronal background K2P channels: focus on TREK1. Nat Rev Neurosci. 2007;8:251-61 pubmed
    ..Recent in vivo studies have demonstrated that TREK1, the most thoroughly studied K(2P) channel, has a key role in the cellular mechanisms of neuroprotection, anaesthesia, pain and depression. ..
  42. Bayliss D, Sirois J, Talley E. The TASK family: two-pore domain background K+ channels. Mol Interv. 2003;3:205-19 pubmed
  43. Honore E, Patel A, Chemin J, Suchyna T, Sachs F. Desensitization of mechano-gated K2P channels. Proc Natl Acad Sci U S A. 2006;103:6859-64 pubmed
    ..Desensitization and its regulation by chemical messengers is predicted to condition the physiological role of K2P channels. ..
  44. Graham V, Zhang H, Willis S, Creazzo T. Expression of a two-pore domain K+ channel (TASK-1) in developing avian and mouse ventricular conduction systems. Dev Dyn. 2006;235:143-51 pubmed
    ..Our results are consistent with a common mechanism for ventricular conduction system development in avians and mammals, despite differences in the anatomy of the mature conduction systems of these organisms. ..
  45. Kim D. Physiology and pharmacology of two-pore domain potassium channels. Curr Pharm Des. 2005;11:2717-36 pubmed
    ..Therefore, K2P channels could become potentially important therapeutic targets for the treatment of various pathological conditions. ..
  46. Chemin J, Patel A, Duprat F, Lauritzen I, Lazdunski M, Honore E. A phospholipid sensor controls mechanogating of the K+ channel TREK-1. EMBO J. 2005;24:44-53 pubmed
    ..Protonation of E306 drastically tightens channel-phospholipid interaction and leads to TREK-1 opening at atmospheric pressure. The TREK-1-phospholipid interaction is critical for channel mechano-, pH(i)- and voltage-dependent gating. ..
  47. Kang D, Han J, Talley E, Bayliss D, Kim D. Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. J Physiol. 2004;554:64-77 pubmed
    ..These electrophysiological studies show that native 38 pS K+ channels of the TASK family in cultured CG neurones consist of both homomeric TASK-3 and heteromeric TASK-1/TASK-3. ..
  48. Kim D. Fatty acid-sensitive two-pore domain K+ channels. Trends Pharmacol Sci. 2003;24:648-54 pubmed
    ..The unique properties of K(FA) channels indicate that they are well suited to sensing various types of stress that occur in the cell. ..
  49. Chemin J, Girard C, Duprat F, Lesage F, Romey G, Lazdunski M. Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels. EMBO J. 2003;22:5403-11 pubmed
    ..Mechanisms described here with group I mGluRs will also probably stand for many other receptors of hormones and neurotransmitters. ..
  50. Goldstein S, 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 pubmed
    ..Even though two-P-domain channels are widespread and essential, they were hidden from sight in plain view--our most basic questions remain to be answered. ..
  51. Buckler K, Williams B, Honore E. An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. J Physiol. 2000;525 Pt 1:135-42 pubmed
    ..Using in situ hybridisation TASK-1 mRNA was found to be expressed in type-I cells. We conclude that the oxygen- and acid-sensitive background K+ channel of carotid body type-I cells is likely to be an endogenous TASK-1-like channel. ..
  52. 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 pubmed
    ..TASK-3 was blocked by barium (57%, 3 mM), quinidine (37%, 100 microM), and lidocaine (62%, 1 mM). Thus, TASK-3 is a new member of the acid-sensing K(+) channel subfamily (TASK). ..
  53. 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 pubmed
    ..7 and only 10% at pH 6.7. This property is probably essential for its physiological function, and suggests that small pH variations may serve a communication role in the nervous system. ..