Skip to main content

Advertisement

SpringerLink
Log in

Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels

  • Original paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The mammalian family of two-pore domain K+ (K2P) channel proteins are encoded by 15 KCNK genes and subdivided into six subfamilies on the basis of sequence similarities: TWIK, TREK, TASK, TALK, THIK, and TRESK. K2P channels are expressed in cells throughout the body and have been implicated in diverse cellular functions including maintenance of the resting potential and regulation of excitability, sensory transduction, ion transport, and cell volume regulation, as well as metabolic regulation and apoptosis. In recent years K2P channel isoforms have been identified as important targets of several widely employed drugs, including: general anesthetics, local anesthetics, neuroprotectants, and anti-depressants. An important goal of future studies will be to identify the basis of drug actions and channel isoform selectivity. This goal will be facilitated by characterization of native K2P channel isoforms, their pharmacological properties and tissue-specific expression patterns. To this end the present review examines the biophysical, pharmacological, and functional characteristics of cloned mammalian K2P channels and compares this information with the limited data available for native K2P channels in order to determine criteria which may be useful in identifying ionic currents mediated by native channel isoforms and investigating their pharmacological and functional characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aimond, F., Rauzier, J.-M., Bony, C., & Vassort, G. (2000). Simultaneous activation of p38 MAPK and p42/44 MAPK by ATP stimulates the K+ current ITREK in cardiomyocytes. Journal of Biological Chemistry, 275, 39110–39116.

    PubMed  CAS  Google Scholar 

  2. Aller, M. I., Veale, E. L., Linden, A.-M., Sandu, C., Schwaninger, M., Evans, L. J., Korpi, E. R., Mathie, A., Wisden, W., & Brickley, S. G. (2005). Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons. The Journal of Neuroscience, 25, 11455–11467.

    PubMed  CAS  Google Scholar 

  3. Alloui, A., Zimmermann, K., Mamet, J., Duprat, J., Noel, J., Chemin, J., Guy, N., Blondeau, N., Voilley, N., Rubat-Coudert, C., Borsotto, M., Romey, G., Heurteaux, C., Reeh, P., Eschalier, A., & Lazdunski, M. (2006). TREK-1, a K+ channel involved in polymodal pain perception. EMBO Journal, 25, 2368–2376.

    PubMed  CAS  Google Scholar 

  4. Arrighi, I., Lesage, F., Scimeca, J.-C., Carle, G. F., & Barhanin, J. (1998). Structure, chromosome localization, and tissue distribution of the mouse twik K+ channel gene. FEBS Letters, 425, 310–316.

    PubMed  CAS  Google Scholar 

  5. Ashmole, I., Goodwin, P. A., & Stanfield, P. R. (2001). TASK-5, a novel member of the tandem pore K+ channel family. Pflügers Archiv, 44, 828–833.

    Google Scholar 

  6. Bang, H., Kim, Y., & Kim, D. (2000). TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. Journal of Biological Chemistry, 275, 17412–17419.

    PubMed  CAS  Google Scholar 

  7. Barbuti, A., Ishii, S., Shimizu, T., Robinson, R. B., & Feinmark, S. J. (2002). Block of the background K+ channel TASK-1 contributes to arrhythmogenic effects of platelet-activating factor. American Journal of Physiology. Heart and Circulatory Physiology, 282, H2024–H2030.

    PubMed  CAS  Google Scholar 

  8. Barriere, H., Belfodil, R., Rubera, I., Tauc, M., Lesage, F., Poujeol, C., Guy, N., Barhanin, J., & Poujeol, P. (2003). Role of TASK2 potassium channels regarding volume regulation in primary cultures of mouse proximal tubules. The Journal of General Physiology, 122, 177–190.

    PubMed  CAS  Google Scholar 

  9. Bayliss, D. A., Sirois, J. E., & Talley, E. M. (2003). The TASK family: Two-pore domain background K+ channels. Molecular Interventions, 3, 205–219.

    PubMed  CAS  Google Scholar 

  10. Berg, A. P., Talley, E. M., Manger, J. P., & Bayliss, D. A. (2004). Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits. The Journal of Neuroscience, 24, 6693–6702.

    PubMed  CAS  Google Scholar 

  11. Besana, A., Barbuti, A., Tateyama, M. A., Symes, A. J., Robinson, R. B., & Feinmark, S. J. (2004). Activation of protein kinase C ε inhibits the two-pore domain K+ channel, TASK-1, inducing repolarization abnormalities in cardiac ventricular myocytes. Journal of Biological Chemistry, 279, 33154–33160.

    PubMed  CAS  Google Scholar 

  12. Blondeau, N., Lauritzen, I., Widmann, C., Lazdunski, M., & Heurteaux, C. (2002). A potent protective role of lysophospholipids against global cerebral ischemia and glutamate excitotoxicity in neuronal cultures. Journal of Cerebral Blood Flow and Metabolism, 22, 821–834.

    PubMed  CAS  Google Scholar 

  13. Blondeau, N., Widmann, C., Lazdunski, M., & Heurteaux, C. (2001). Polyunsaturated fatty acids induce ischemic and epileptic tolerance. Neuroscience, 109, 231–241.

    Google Scholar 

  14. Bockenhauer, D., Nimmakavalu, M. A., Ward, D. C., Goldstein, S. A., & Gallagher, P. G. (2000). Genomic organization and chromosomal localization of the murine 2P domain potassium channel Knck8: Conservation of gene structure in 2 P domain channels. Gene, 261, 365–372.

    PubMed  CAS  Google Scholar 

  15. Bockenhauer, D., Zilberberg, N., & Goldstein, S. A. N. (2001). KCNK2: Reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nature Neuroscience, 4, 486–491.

    PubMed  CAS  Google Scholar 

  16. Boyd, D. F., Millar, J. A., Watkins, C. S., & Mathie, A. (2000). The role of Ca2+ stores in the muscarinic inhibition of the K+ current IK(SO) in neonatal rat cerebellar granule cells. The Journal of Physiology, 529, 321–331.

    PubMed  CAS  Google Scholar 

  17. Brazier, S. P., Mason, H. S., Bateson, A. N., & Kemp, P. J. (2005). Cloning of the human TASK-2 (KCNK5) promoter and its regulation by chronic hypoxia. Biochemical and Biophysical Research Communications, 336, 1251–1258.

    PubMed  CAS  Google Scholar 

  18. Buckler, K. J., & Honoré, E. (2005). The lipid-activated two-pore domain K+ channel TREK-1 is resistant to hypoxia: Implications for ischaemic neuroprotection. The Journal of Physiology, 562, 213–222.

    PubMed  CAS  Google Scholar 

  19. Buckler, K. J., Williams, B. A., & Honoré, E. (2000). An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. The Journal of Physiology, 525, 135–142.

    PubMed  CAS  Google Scholar 

  20. Burg, E. D., Remillard, C. V., & Yaun, J. X.-J. (2006). K+ channels in apoptosis. Journal of Membrane Biology, 209, 1–18.

    Google Scholar 

  21. Caley, A. J., Gruss, M., & Franks, N. P. (2005). The effects of hypoxia on the modulation of human TREK-1 potassium channels. The Journal of Physiology, 562, 205–212.

    PubMed  CAS  Google Scholar 

  22. Campanucci, V. A., Brown, S. T., Hudasek, K., O’Kelly, I. M., Nurse, C. A., & Fearon, I. M. (2005). O2 sensing by recombinant TWIK-related halothane-inhibitable K+ channel-1 background K+ channels heterologously expressed in human embryonic kidney cells. Neuroscience, 135, 1087–1094.

    PubMed  CAS  Google Scholar 

  23. Chavez, R. A., Gray, A. T., Zhao, B. R., Kindler, C. H., Mazurek, M. J., Mehta, Y., Forsayeth, J. R., & Yost, C. S. (1999). TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family. Journal of Biological Chemistry, 274, 7887–7892.

    PubMed  CAS  Google Scholar 

  24. Chemin, J., Girard, C., Duprat, F., Lesage, F., Romey, G., & Lazdunski, M. (2003). Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels. EMBO Journal, 22, 5403–5411.

    PubMed  CAS  Google Scholar 

  25. Chemin, J., Patel, A. J., Duprat, F., Lauritzen, I., Lazdunski, M., & Honoré, E. (2005). A phospholipid sensor controls mechanogating of the K+ channel TREK-1. EMBO Journal, 24, 44–53.

    PubMed  CAS  Google Scholar 

  26. Chemin, J., Patel, A. J., Duprat, F., Zanzouri, M., Lazdunski, M., & Honoré, E. (2005). Lysophosphatidic acid-operated K+ channels. Journal of Biological Chemistry, 280, 4415–4421.

    PubMed  CAS  Google Scholar 

  27. Chen, X., Talley, E. M., Patel, N., Gomis, A., McIntire, W. E., Dong, B., Viana, F., Garrison, J. C., & Bayliss, D. A. (2006). Inhibition of a background potassium channel by Gq protein α-subunits. Proceedings of the National Academy of Sciences of the United States of America, 103, 3422–3427.

    PubMed  CAS  Google Scholar 

  28. Cho, S. Y., Beckett, E. A., Baker, S. A., Han, I., Park, K. J., Monaghan, K., Ward, S. M., Sanders, K. M., & Koh, S. D. (2005). A pH-sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract. The Journal of Physiology, 565, 243–259.

    PubMed  CAS  Google Scholar 

  29. Chvanov, M., Petersen, O. H., & Tepikin, A. (2005). Free radicals and the pancreatic acinar cells: Role in physiology and pathology. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 360, 2273–2284.

    PubMed  CAS  Google Scholar 

  30. Clarke, E. C., Veale, E. L., Green, P. J., Meadows, H. J., & Mathie, A. (2004). Selective block of the human 2-P domain potassium channel, TASK-3, and native leak potassium current, IKSO, by zinc. Journal of Physiology, 560, 51–62.

    PubMed  CAS  Google Scholar 

  31. Cotten, J. F., Zou, H. L., Liu, C., Au, J. D., & Yost, C. S. (2004). Identification of native rat cerebellar granule cell currents due to background K channel KCNK5 (TASK-2). Molecular Brain Research, 128, 112–120.

    PubMed  CAS  Google Scholar 

  32. Czirjak, G., & Enyedi, P. (2002). TASK-3 dominates the background potassium conductance in rat adrenal glomerulosa cells. Molecular Endocrinology, 16, 621–629.

    PubMed  CAS  Google Scholar 

  33. Czirjak, G., & Enyedi, P. (2002). Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits. Journal of Biological Chemistry, 277, 5426–5432.

    PubMed  CAS  Google Scholar 

  34. Czirjak, G., & Enyedi, P. (2003). Ruthenium red inhibits TASK-3 potassium channel by interconnecting glutamate 70 of the two subunits. Molecular Pharmacology, 63, 646–652.

    PubMed  CAS  Google Scholar 

  35. Czirjak, G., & Enyedi, P. (2006). Targeting of calcineurin to an NFAT-like docking site is required for the calcium-dependent activation of the background K+ channel, TRESK. Journal of Biological Chemistry, 281, 14677–14682.

    PubMed  CAS  Google Scholar 

  36. Czirjak, G., & Enyedi, P. (2006). Zinc and mercuric ions distinguish TRESK from the other two-pore-domain K+ channels. Molecular Pharmacology, 69, 1024–1032.

    PubMed  CAS  Google Scholar 

  37. Czirjak, G., Petheo, G. L., Spat, A., & Enyedi, P. (2001). Inhibition of TASK-1 potassium channel by phospholipase C. American Journal of Physiology. Cell Physiology, 281, C700–C708.

    PubMed  CAS  Google Scholar 

  38. Czirjak, G., Toth, Z. E., & Enyedi, P. (2004). The two-pore domain K+ channel, TRESK, is activated by the cytoplasmic calcium signal through calcineurin. Journal of Biological Chemistry, 279, 18550–18558.

    PubMed  CAS  Google Scholar 

  39. Danthi, S., Enyeart, J. A., & Enyeart, J. J. (2003). Modulation of native TREK-1 and Kv1.4 K+ channels by polyunsaturated fatty acids and lysophospholipids. Journal of Membrane Biology, 195, 147–164.

    PubMed  CAS  Google Scholar 

  40. Davis, K. A., & Cowley, E. A. (2006). Two-pore-domain potassium channels support anion secretion from human airway Calu-3 epithelial cells. Pflügers Archiv, 451, 631–641.

    PubMed  CAS  Google Scholar 

  41. Decher, N., Maier, M., Dittrich, W., Gassenhuber, J., Bruggemann, A., Busch, A. E., & Steinmeyer, K. (2001). Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family. FEBS Letters, 492, 84–89.

    PubMed  CAS  Google Scholar 

  42. Decressac, S., Franco, M., Bendahhou, S., Warth, R., Knauer, S., Barhanin, J., Lazdunski, M., & Lesage, F. (2004). ARF6-dependent interaction of the TWIK1 K+ channel with EFA6, a GDP/GTP exchange factor for ARF6. EMBO Reports, 5, 1171–1175.

    PubMed  CAS  Google Scholar 

  43. Doyle, D. A., Cabrial, J. M., Pfeutzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., & MacKinnon, R. (1998). The structure of the potassium channel: Molecular basis of K+ conduction and selectivity. Science, 280, 69–77.

    PubMed  CAS  Google Scholar 

  44. Duprat, F., Girard, C., Jarretou, G., & Lazdunski, M. (2005). Pancreatic two P domain K+ channels TALK-1 and TALK-2 are activated by nitric oxide and reactive oxygen species. The Journal of Physiology, 562, 235–244.

    PubMed  CAS  Google Scholar 

  45. Duprat, F., Lesage, F., Fink, M., Reyes, R., Heurteaux, C., & Lazdunski, M. (1997). TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO Journal, 16, 5464–5471.

    PubMed  CAS  Google Scholar 

  46. Duprat, F., Lesage, F., Patel, A. J., Fink, M., Romey, G., & Lazdunski, M. (2000). The neuroprotective agent riluzole activates the two P domain K+ channels TREK-1 and TRAAK. Molecular Pharmacology, 57, 906–912.

    PubMed  CAS  Google Scholar 

  47. Enyeart, J. A., Danthi, S., & Enyeart, J. J. (2004). TREK-1 K+ channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells. American Journal of Physiology. Endocrinology and Metabolism, 287, E1154–E1165.

    PubMed  CAS  Google Scholar 

  48. Enyeart, J. J., Gomora, J. C., Xu, L., & Enyeart, J. A. (1997). Adenosine triphosphate activates a noninactivating K+ current in adrenal cortical cells through nonhydrolytic binding. The Journal of General Physiology, 110, 679–692.

    PubMed  CAS  Google Scholar 

  49. Enyeart, J. J., Mlinar, B., & Enyeart, J. A. (1996). Adrenocorticotropic hormone and cAMP inhibit noninactivating K+ current in adrenocortical cells by an A-kinase-independent mechanism requiring ATP hydrolysis. The Journal of General Physiology, 108, 251–264.

    PubMed  CAS  Google Scholar 

  50. Enyeart, J. J., Xu, L., Danthi, S., & Enyeart, J. A. (2002). An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1. Journal of Biological Chemistry, 277, 49186–49199.

    PubMed  CAS  Google Scholar 

  51. Fink, M., Duprat, F., Lesage, F., Reyes, R., Romey, G., Heurteaux, C., & Lazdunski, M. (1996). Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO Journal, 15, 6854–6862.

    PubMed  CAS  Google Scholar 

  52. Fink, M., Lesage, F., Duprat, F., Heurteaux, C., Reyes, R., Fosset, M., & Lazdunski, M. (1998). A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO Journal, 17, 3297–3308.

    PubMed  CAS  Google Scholar 

  53. Fong, P., Argent, B. E., Guggino, W. B., & Gray, M. A. (2003). Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF. American Journal of Physiology. Cell Physiology, 285, C433–C445.

    PubMed  CAS  Google Scholar 

  54. Franks, N. P., & Honoré, E. (2004). The TREK K2P channels and their role in general anesthesia and neuroprotection. Trends in Pharmacological Sciences, 25, 601–608.

    PubMed  CAS  Google Scholar 

  55. Gabriel, A., Abdallah, M., Yost, C. S., Winegar, B. D., & Kindler, C. H. (2002). Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat central nervous system. Molecular Brain Research, 98, 153–163.

    PubMed  CAS  Google Scholar 

  56. Gardener, M. J., Johnson, I. T., Burnham, M. P., Edwards, G., Heagerty, A. M., & Weston, A. H. (2004). Functional evidence of a role for two-pore domain potassium channels in rat mesenteric and pulmonary arteries. British Journal of Pharmacology, 142, 192–202.

    PubMed  CAS  Google Scholar 

  57. Gerstin, K. M., Gong, D. H., Abdallah, M., Winegar, B. D., Eger II, E. I., & Gray, A. T. (2003). Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration. Anesthesia and Analgesia, 96, 1345–1349.

    PubMed  CAS  Google Scholar 

  58. Girard, C., Duprat, F., Terrenoire, C., Tinel, N., Fosset, M., Romey, G., Lazdunski, M., & Lesage, F. (2001). Genomic and functional characteristics of novel human pancreatic 2P domain K+ channels. Biochemical and Biophysical Research Communications, 282, 249–256.

    PubMed  CAS  Google Scholar 

  59. Girard, C., Tinel, N., Terrenoire, C., Romey, G., Lazdunski, M., & Borsotto, M. (2002). p11, an annexin II subunit, an auxiliary protein associated with the background K+ channel, TASK-1. EMBO Journal, 21, 4439–4448.

    PubMed  CAS  Google Scholar 

  60. Gnatenco, C., Han, J., Snyder, A. K., & Kim, D. (2002). Functional expression of TREK-2 K+ channel in cultured rat brain astrocytes. Brain Research, 931, 56–67.

    PubMed  CAS  Google Scholar 

  61. Goldstein, S. A. N., Bockenhauer, D., O’Kelly, I., & Zilberberg, N. (2001). Potassium leak channels and the KCNK family of two-P-domain subunits. Nature Reviews. Neuroscience, 2, 175–184.

    PubMed  CAS  Google Scholar 

  62. Goldstein, S. A. N., Wang, K.-W., Ilan, N., & Pausch, M. (1998). Sequence and function of the two P domain potassium channels: Implications of an emerging superfamily. Journal of Molecular Medicine, 76, 13–20.

    PubMed  CAS  Google Scholar 

  63. Gomora, J. C., & Enyeart, J. J. (1999). Dual pharmacological properties of a cyclic AMP-sensitive potassium channel. The Journal of Pharmacology and Experimental Therapeutics, 290, 266–275.

    PubMed  CAS  Google Scholar 

  64. Gomora, J. C., Enyeart, J. A., & Enyeart, J. J. (1999). Mibefradil potently blocks ATP-activated K+ channels in adrenal cells. Molecular Pharmacology, 56, 1192–1197.

    PubMed  CAS  Google Scholar 

  65. Gonczi, M., Szentandrassy, N., Johmson, I. T., Heagerty, A. M., & Weston, A. H. (2006). Investigation of the role of TASK-2 channels in rat pulmonary arteries; pharmacological and functional studies following RNA interference procedures. British Journal of Pharmacology, 147, 496–505.

    PubMed  Google Scholar 

  66. 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. (2000). Volatile anesthetics activate the human tandem pore domain baseline K+ channel KNCK5. Anesthesiology, 92, 1722–1730.

    PubMed  CAS  Google Scholar 

  67. Grus, M., Bushell, T. J., Bright, D. P., Lieb, W. R., Mathies, A., & Franks, N. P. (2004). Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide and cyclopropane. Molecular Pharmacology, 65, 443–452.

    Google Scholar 

  68. Grus, M., Mathie, A., Lieb, W. R., & Franks, N. P. (2004). The two-pore-domain K+ channels TREK-1 and TASK-3 are differentially modulated by copper and zinc. Molecular Pharmacology, 66, 530–537.

    Google Scholar 

  69. Gu, W., Schlichthörl, G., Hirsch, J. R., Engels, H., Karschin, C., Karschin, A., Derst, C., Steinlein, O., & Daut, J. (2002). Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. The Journal of Physiology, 539, 657–668.

    PubMed  CAS  Google Scholar 

  70. Gurney, A. M., Psipenko, O. N., MacMillan, D., McFarlane, K. M., Tate, R. J., & Kempsil, F. E. J. (2003). Two-pore domain K channel, TASK-1, in pulmonary artery smooth muscle cells. Circulation Research, 93, 957–964.

    PubMed  CAS  Google Scholar 

  71. Gutman, G. A., et al. (2003). International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: Potassium channels. Pharmacological Reviews, 55(4), 583–586.

    PubMed  CAS  Google Scholar 

  72. Hajdu, P., Ulens, C., Panyi, G., & Tytgat, J. (2003). Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K+ channel. Cardiovascular Research, 58, 46–54.

    PubMed  CAS  Google Scholar 

  73. Hamill, O. P., & Martinac, B. (2001). Molecular basis of mechanotransduction in living cells. Physiological Reviews, 81, 685–740.

    PubMed  CAS  Google Scholar 

  74. Han, J., Gnatenco, C., Sladek, C. D., & Kim, D. (2003). Background and tandem-pore potassium channels in magnocellular neurosecretory cells of the rat supraoptic nucleus. The Journal of Physiology, 546, 625–639.

    PubMed  CAS  Google Scholar 

  75. Han, J., Kang, D., & Kim, D. (2003). Functional properties of four splice variants of a human pancreatic tandem-pore K+ channel, TALK-1. American Journal of Physiology. Cell Physiology, 285, C529–C538.

    PubMed  CAS  Google Scholar 

  76. Han, J., Truell, J., Gnatenco, C., & Kim, D. (2002). Characterization of four types of background potassium channels in rat cerebellar granule neurons. The Journal of Physiology, 542, 431–444.

    PubMed  CAS  Google Scholar 

  77. Harinath, S., & Sikdar, S. K. (2004). Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels. Neuropharmacology, 46, 750–760.

    PubMed  CAS  Google Scholar 

  78. Hartness, M. E., Lewis, A., Searle, G. J., O’Kelly, I., Peers, C., & Kemp, P. J. (2001). Combined antisense and pharmacological approaches implicate hTASK as an airway O2 sensing K+ channel. Journal of Biological Chemistry, 276, 26499–26508.

    PubMed  CAS  Google Scholar 

  79. Hervieu, G. J., Cluderay, J. E., Gray, C. W., Green, P. J., Ranson, J. L., Randall, A. D., & Meadows, H. J. (2001). Distribution and expression of TREK-1, a two-pore-domain potassium channel in the adult rat CNS. Neuroscience, 103, 899–919.

    PubMed  CAS  Google Scholar 

  80. Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang-Lazdunski, L., Widmann, C., Zanzouri, M., Romey, G., & Lazdunski, M. (2004). TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO Journal, 23, 2684–2695.

    PubMed  CAS  Google Scholar 

  81. Heurteaux, C., Laigle, C., Blondeau, N., Jarretou, G., & Lazdunski, M. (2006). Alpha-linolenic acid and riluzole treatment confer cerebral protection and improve survival after focal brain ischemia. Neuroscience, 137, 241–251.

    PubMed  CAS  Google Scholar 

  82. Heurteaux, C., Lucas, G., Guy, N., Yacoubi, M. E., Thummler, S., Peng, X.-D., Noble, F., Blondeau, N., Widmann, C., Borsotto, M., Gobbi, G., Vaugeois, J.-M., Debonnel, G., & Lazdunski, M. (2006). Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nature Neuroscience, 9, 1134–1141.

    PubMed  CAS  Google Scholar 

  83. Hille, B. (2001). Ion channels of excitable membranes. Sunderland, MA: Sinauer.

    Google Scholar 

  84. Honoré, E., Maingret, F., Lazdunski, M., & Patel, A. J. (2002). An intracellular proton sensor commands lipid- and mechano-gating of the K+ channel TREK-1. EMBO Journal, 21, 2968–2976.

    PubMed  Google Scholar 

  85. Honoré, E., Patel, A. J., Chemin, J., Suchyna, T., & Sachs, F. (2006). Desensitization of mechano-gated K2P channels. Proceedings of the National Academy of Sciences of the United States of America, 103, 6859–6864.

    PubMed  Google Scholar 

  86. Hsu, K., Seharaseyon, J., Dong, P., Bour, S., & Marban, E. (2004). Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Molecular Cell, 14, 259–267.

    PubMed  CAS  Google Scholar 

  87. Ilan, N., & Goldstein, S. A. N. (2001). KCNKø: Single, cloned potassium leak channels are multi-ion pores. Biophysical Journal, 80, 241–253.

    Article  PubMed  CAS  Google Scholar 

  88. Kang, D., Choe, C., & Kim, D. (2004). Functional expression of TREK-2 in insulin-secreting MIN6 cells. Biochemical and Biophysical Research Communications, 323, 323–331.

    PubMed  CAS  Google Scholar 

  89. Kang, D., Choe, C., & Kim, D. (2005). Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. The Journal of Physiology, 564, 103–116.

    PubMed  CAS  Google Scholar 

  90. Kang, D., Han, J., Talley, E. M., Bayliss, D. A., & Kim, D. (2003). Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. The Journal of Physiology, 554, 64–77.

    Google Scholar 

  91. Kang, D., & Kim, D. (2004). Single-channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family. Biochemical and Biophysical Research Communications, 315, 836–844.

    PubMed  CAS  Google Scholar 

  92. Kang, D., & Kim, D. (2006). TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons. American Journal of Physiology. Cell Physiology, 291, C138–C146.

    PubMed  CAS  Google Scholar 

  93. Kang, D., La, J.-H., Kim, E.-J., Park, J.-Y., Hong, S.-G., & Han, J. (2006). An endogenous acid-sensitive K+ channel expressed in COS-7 cells. Biochemical and Biophysical Research Communication, 341, 1231–1236.

    CAS  Google Scholar 

  94. Kang, D., Mariash, E., & Kim, D. (2004). Functional expression of TRESK-2, a new member of the tandem-pore K+ channels family. Journal of Biological Chemistry, 279, 28063–28070.

    PubMed  CAS  Google Scholar 

  95. Karschin, C., Wischmeyer, E., Preisig-Müller, R., Rajan, S., Derst, C., Grzeschik, K.-H., Daut, J., & Karschin, A. (2001). 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. Molecular and Cellular Neurosciences, 18, 632–648.

    PubMed  CAS  Google Scholar 

  96. Kemp, P. J., Searle, G. J., Hartness, M. E., Lewis, A., Miller, P., Williams, S., Wootton, P., Adriaensen, D., & Peers, C. (2003). Acute oxygen sensing in cellular models: Relevance to the physiology of pulmonary neuroepithelial and carotid bodies. The Anatomical Record, 270A, 41–50.

    CAS  Google Scholar 

  97. Kennard, L. E., Chumbley, J. R., Ranatunga, K. M., Armstrong, S. J., Veale, E. L., & Mathie, A. (2005). Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine. British Journal of Pharmacology, 144, 821–829.

    PubMed  CAS  Google Scholar 

  98. Keshavaprasad, B., Liu, C., Au, J. D., Kindler, C. H., Cotten, J. F., & Yost, C. S. (2005). Species-specific differences in response to anesthetics and other modulators by the K2P channel TRESK. Anesthesia and Analgesia, 101, 1042–1049.

    PubMed  CAS  Google Scholar 

  99. Ketchum, K. A., Joiner, W. J., Sellers, A. J., Kaczmarek, L. K., & Goldstein, S. A. N. (1995). A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature, 376, 690–695.

    PubMed  CAS  Google Scholar 

  100. Kim, D. (2005). Physiology and pharmacology of two-pore domain potassium channels. Current Pharmaceutical Design, 11, 2717–2736.

    PubMed  CAS  Google Scholar 

  101. Kim, Y., Bang, H., Gnatenco, C., & Kim, D. (2001). Synergistic interaction and the role of C-terminus in activation of TRAAK K+ channels by pressure, free fatty acids and alkali. Pflügers Archiv, 442, 64–72.

    PubMed  CAS  Google Scholar 

  102. Kim, Y., Bang, H., & Kim, D. (1999). TBAK-1 and TASK-1, two-pore K+ channel subunits: Kinetic properties and expression in rat heart. American Journal of Physiology. Heart and Circulatory Physiology, 277, H1669–H1678.

    CAS  Google Scholar 

  103. Kim, Y., Bang, H., & Kim, D. (2000). TASK-3, a new member of the tandem pore K+ channel family. Journal of Biological Chemistry, 275, 9340–9347.

    PubMed  CAS  Google Scholar 

  104. Kim, D., & Gnatenco, C. (2001). TASK-5, a new member of the tandem-pore K+ channel family. Biochemical and Biophysical Research Communications, 284, 923–930.

    PubMed  CAS  Google Scholar 

  105. Kim, Y., Gnatenco, C., Bang, H., & Kim, D. (2001). Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi. Pflügers Archiv, 442, 952–960.

    PubMed  CAS  Google Scholar 

  106. Kim, J.-S., Park, J.-Y., Kang, H.-W., Lee, E.-J., Bang, H., & Lee, J.-H. (2005). Zinc activates TREK-2 potassium channel activity. The Journal of Pharmacology and Experimental Therapeutics, 314, 618–625.

    PubMed  CAS  Google Scholar 

  107. Kindler, C. H., Paul, M., Zou, H., Liu, C., Winegar, B. D., Gray, A. T., & Yost, C. S. (2003). Amide local anesthetics potently inhibit the human tandem pore domain background K+ channel TASK-2 (KCNK5). The Journal of Pharmacology and Experimental Therapeutics, 306, 84–92.

    PubMed  CAS  Google Scholar 

  108. Kindler, C. H., Yost, C. S., & Gray, A. T. (1999). Local anesthetic inhibition of baseline potassium channels with two pore domains in tandem. Anesthesiology, 90, 1092–1102.

    PubMed  CAS  Google Scholar 

  109. Koh, S. D., Monaghan, K., Sergeant, G. P., Ro, S., Walker, R. L., Sanders, K. M., & Horowitz, B. (2001). TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. Journal of Biological Chemistry, 276, 44338–44346.

    PubMed  CAS  Google Scholar 

  110. Kung, C. (2005). A possible unifying principle for mechanosensation. Nature, 436, 647–654.

    PubMed  CAS  Google Scholar 

  111. Lauritzen, I., Blondeau, N., Heurteaux, C., Widmann, C., Romey, G., & Lazdunski, M. (2000). Polyunsaturated fatty acids are potent neuroprotectors. EMBO Journal, 19, 1784–1793.

    PubMed  CAS  Google Scholar 

  112. Lauritzen, I., Chemin, J., Honoré, E., Jodar, M., Guy, N., Lazdunski, M., & Patel, A. J. (2005). Cross-talk between the mechano-gated K2P channel TREK-1 and the actin cytoskeleton. EMBO Reports, 6, 642–648.

    PubMed  CAS  Google Scholar 

  113. Lauritzen, I., Zanzouri, M., Honoré, E., Duprat, F., Ehrengruber, M. U., Lazdunski, M., & Patel, A. J. (2003). K+-dependent cerebellar granule neuron apoptosis: Role of TASK leak K+ channels. Journal of Biological Chemistry, 278, 32068–32076.

    PubMed  CAS  Google Scholar 

  114. Leonoudakis, D., Gray, A. T., Winegar, B. D., Kindler, C. H., Harada, M., Taylor, D. M., Chavez, R. A., Forsayeth, J. R., & Yost, C. S. (1998). An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. Journal of Neuroscience, 18, 868–877.

    PubMed  CAS  Google Scholar 

  115. Lesage, F. (2003). Pharmacology of neuronal background potassium channels. Neuropharm, 44, 1–7.

    CAS  Google Scholar 

  116. Lesage, F., Guillemare, E., Fink, M., Duprat, F., Lazdunski, M., Romey, G., & Barhanin, J. (1996). A pH sensitive yeast outward rectifier K+ channel with two pore domains and novel gating properties. The Journal of Biological Chemistry, 271, 4183–4187.

    PubMed  CAS  Google Scholar 

  117. Lesage, F., Guillemare, E., Fink, M., Duprat, F., Lazdunski, M., Romey, G., & Barhanin, J. (1996). TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO Journal, 15, 1004–1011.

    PubMed  CAS  Google Scholar 

  118. Lesage, F., Lauritzen, I., Duprat, F., Reyes, R., Fink, M., Heurteaux, C., & Lazdunski, M. (1997). The structure, function and distribution of the mouse TWIK-1 K+ channel. FEBS Letters, 402, 28–32.

    PubMed  CAS  Google Scholar 

  119. Lesage, F., & Lazdunski, M. (2000). Molecular and functional properties of two-pore-domain potassium channels. American Journal of Physiology. Renal Physiology, 279, F793–F801.

    PubMed  CAS  Google Scholar 

  120. Lesage, F., Reyes, R., Fink, M., Duprat, F., Guillemare, E., & Lazdunski, M. (1996). Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge. EMBO Journal, 15, 6400–6407.

    PubMed  CAS  Google Scholar 

  121. Lesage, F., Terrenoire, C., Romey, G., & Lazdunski, M. (2000). Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. Journal of Biological Chemistry, 275, 28398–28405.

    PubMed  CAS  Google Scholar 

  122. Lewis, A., Hartness, M. E., Chapman, C. G., Fearon, I. M., Meadows, H. J., Peer, C., & Kemp, P. J. (2001). Recombinant hTASK1 is an O2-sensitive K+ channel. Biochemical and Biophysical Research Communications, 285, 1290–1294.

    PubMed  CAS  Google Scholar 

  123. Li, X. T., Dyachenko, V., Zuzarte, M., Putzke, C., Preisig-Muller, R., Isenberg, G., & Daut, J. (2006). The stretch-activated potassium channel TREK-1 in rat cardiac ventricular muscle. Cardiovascular Research, 69, 86–97.

    Google Scholar 

  124. Lin, W., Burks, C. A., Hansen, D. R., Kinnamon, S. C., & Gilbertson, T. A. (2004). Taste receptor cells express pH-sensitive leak K+ channels. Journal of Neurophysiology, 92, 2909–2919.

    PubMed  CAS  Google Scholar 

  125. Linden, A.-M., Aller, M. I., Leppa, E., Vekovischeva, O., Aitta-aho, T., Veale, E. L., Mathie, A., Rosenberg, P., Wisden, W., & Korpi, E. R. (2006). The in vivo contributions of TASK-1-containing channels to the actions of inhalation anesthetics, the α2 adrenergic sedative dexmedetomidine, and cannabinoid agonists. The Journal of Pharmacology and Experimental Therapeutics, 317, 615–626.

    PubMed  CAS  Google Scholar 

  126. Liu, C., Au, J. D., Zou, H. L., Cotten, J. F., & Yost, C. S. (2004). Potent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics. Anesthesia and Analgesia, 99, 1715–1722.

    PubMed  CAS  Google Scholar 

  127. Liu, C., Cotton, J. F., Schuyler, J. A., Fahlman, C. S., Au, J. D., Bickler, P. E., & Yost, C. S. (2005). Protective effects of TASK-3 (KCNK9) and related 2P K channels during cellular stress. Brain Research, 1031, 164–173.

    PubMed  CAS  Google Scholar 

  128. Liu, W., & Saint, D. A. (2004). Heterogenous expression of tandem-pore K+ channel genes in adult and embryonic rat heart quantified by real-time polymerase chain reaction. Clinical and Experimental Pharmacology & Physiology, 31, 174–178.

    CAS  Google Scholar 

  129. Long, S. B., Campbell, E. B., & MacKinnon, R. (2005). Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science, 309, 897–903.

    PubMed  CAS  Google Scholar 

  130. Lopes, C. M. B., Gallagher, P. G., Buck, M. E., Butler, M. H., & Goldstein, S. A. N. (2000). Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. Journal of Biological Chemistry, 275, 16969–16978.

    PubMed  CAS  Google Scholar 

  131. Lopes, C. M. B., Rohacs, T., Balla, T., Enyedi, P., & Logothetis, D. E. (2005). PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two pore domain K+ channels. The Journal of Physiology, 564, 117–129.

    PubMed  CAS  Google Scholar 

  132. Lopes, C. M. B., Zilberberg, N., & Goldstein, S. A. N. (2001). Block of Kcnk3 by protons: Evidence that 2-P-domain potassium channel subunits function as homodimers. Journal of Biological Chemistry, 276, 24449–24452.

    PubMed  CAS  Google Scholar 

  133. Lotshaw, D. P. (1997). Characterization of angiotensin II-regulated K+ conductance in rat adrenal glomerulosa cells. Journal of Membrane Biology, 156, 261–277.

    PubMed  CAS  Google Scholar 

  134. Lotshaw, D. P. (2006). Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells. Journal of Membrane Biology, 210, 51–70.

    PubMed  CAS  Google Scholar 

  135. Maingret, F., Fosset, M., Lesage, F., Lazdunski, M., & Honoré, E. (1999). TRAAK is a mammalian neuronal mechano-gated K+ channel. Journal of Biological Chemistry, 274, 1381–1387.

    PubMed  CAS  Google Scholar 

  136. Maingret, F., Honore, E., Lazdunski, M., & Patel, A. J. (2002). Molecular basis of voltage-dependent gating of TREK-1, a mechano-sensitive K+ channel. Biochemical and Biophysical Research Communications, 292, 339–346.

    PubMed  CAS  Google Scholar 

  137. Maingret, F., Lauritzen, I., Patel, A. J., Heurteaux, C., Reyes, R., Lesage, F., Lazdunski, M., & Honoré, E. (2000). TREK-1 is a heat-activated background K+ channel. EMBO Journal, 19, 2483–2491.

    PubMed  CAS  Google Scholar 

  138. Maingret, F., Patel, A. J., Lazdunski, M., & Honore, E. (2001). The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK-1. EMBO Journal, 20, 47–54.

    PubMed  CAS  Google Scholar 

  139. Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M., & Honoré, E. (1999). Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. Journal of Biological Chemistry, 274, 26691–26696.

    PubMed  CAS  Google Scholar 

  140. Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M., & Honoré, E. (2000). Lysophospholipids open the two-pore domain mechano-gated K+ channels TREK-1 and TRAAK. Journal of Biological Chemistry, 275, 10128–10133.

    PubMed  CAS  Google Scholar 

  141. Meadows, H. J., Benham, C. D., Cairns, W., Gloger, I., Jennings, C., Medhurst, A. D., Murdock, P., & Chapman, C. G. (2000). Cloning, localization and functional expression of the human orthologue of the TREK-1 potassium channel. Pflügers Archiv, 439, 714–722.

    PubMed  CAS  Google Scholar 

  142. Meadows, H. J., Chapman, C. G., Duckworth, D. M., Kelsell, R. E., Murdock, P. R., Nasir, S., Rennie, G., & Randall, A. D. (2001). The neuroprotective agent sipatrigine (BW619C89) potently inhibits the human tandem pore-domain K+ channels TREK-1 and TRAAK. Brain Research, 892, 94–101.

    PubMed  CAS  Google Scholar 

  143. Meadows, H. J., & Randall, A. D. (2001). Functional characterization of human TASK-3, an acid-sensitive two-pore domain potassium channel. Neuropharmacology, 40, 551–559.

    PubMed  CAS  Google Scholar 

  144. Medhurst, A. D., Rennie, G., Chapman, C. G., Meadows, H., Duckworth, M. D., Kelsell, R. E., Gloger, I. I., & Pangalos, M. N. (2001). Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Molecular Brain Research, 86, 101–114.

    PubMed  CAS  Google Scholar 

  145. Meuth, S. G., Budde, T., Kanyshkova, T., Broicher, T., Munsch, T., & Pape, H.-C. (2003). Contribution of TWIK-related acid sensitive K+ channel 1 (TASK-1) and TASK-3 channels to the control of activity modes in thalamocortical neurons. Journal of Neuroscience, 23, 6460–6469.

    PubMed  CAS  Google Scholar 

  146. Millar, J. A., Barratt, L., Southan, A. P., Page, K. M., Fyffe, R. E. W., Robertson, B., & Mathie, A. (2000). A functional role for the two-pore domain potassium channels TASK-1 in cerebellar granule neurons. Proceedings of the National Academy of Sciences of the United States of America, 97, 3614–3618.

    PubMed  CAS  Google Scholar 

  147. Miller, P., Kemp, P. J., Lewis, A., Chapman, C. G., Meadows, H. J., & Peers, C. (2003). Acute hypoxia occludes hTREK-1 modulation: Reevaluation of the potential role of tandem P domain K+ channels in central neuroprotection. The Journal of Physiology, 548, 31–37.

    PubMed  CAS  Google Scholar 

  148. Miller, P., Kemp, P. J., & Peers, C. (2005). Structural requirements of O2 sensing by the human tandem-P domain channel, hTREK1. Biochemical and Biophysical Research Communications, 331, 1253–1256.

    PubMed  CAS  Google Scholar 

  149. Miller, P., Peers, C., & Kemp, P. J. (2004). Polymodal regulation of hTREK1 by pH, arachidonic acid, and hypoxia: Physiological impact in acidosis and alkalosis. American Journal of Physiology. Cell Physiology, 286, C272–C282.

    PubMed  CAS  Google Scholar 

  150. Mlinar, B., Biagi, B. A., & Enyeart, J. J. (1995). Losartan-sensitive AII receptors linked to depolarization-dependent cortisol secretion through a novel signaling pathway. Journal of Biological Chemistry, 270, 20942–20951.

    PubMed  CAS  Google Scholar 

  151. Morton, M. J., Abohamed, A., Sivaprasadarao, A., & Hunter, M. (2005). pH sensing in the two-pore domain K+ channel, TASK2. Proceedings of the National Academy of Sciences of the United States of America, 102, 16102–16106.

    PubMed  CAS  Google Scholar 

  152. Morton, M. J., Chipperfield, S., Abohamed, A., Sivaprasadarao, A., & Hunter, M. (2005). Na+-induced inward rectification in the two-pore domain K+ channel, TASK-2. American Journal of Physiology. Renal Physiology, 288, F162–F169.

    PubMed  CAS  Google Scholar 

  153. Morton, M. J., O’Connell, A. D., Sivaprasadarao, A., & Hunter, M. (2003). Determinants of pH sensing in the two-pore domain K+ channels TASK-1 and -2. Pflügers Archiv, 445, 577–583.

    PubMed  CAS  Google Scholar 

  154. Murbartián, J., Lei, Q., Sando, J. J., & Bayliss, D. A. (2005). Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. Journal of Biological Chemistry, 280, 30175–30184.

    PubMed  Google Scholar 

  155. Musset, B., Meuth, S. G., Liu, G. X., Derst, C., Wegner, S., Pape, H.-C., Budde, T., Preisig-Muller, R., & Daut, J. (2006). Effects of divalent cations and spermine on the K+ channel TASK-3 and on the outward current in thalamic neurons. The Journal of Physiology, 572, 639–657.

    PubMed  CAS  Google Scholar 

  156. Nie, X., Arrighi, I., Kaissling, B., Pfaff, I., Mann, J., Barhanin, J., & Vallon, V. (2005). Expression and insights on function of potassium channel TWIK-1 in mouse kidney. Pflugers Archiv, 451, 479–488.

    PubMed  CAS  Google Scholar 

  157. Niemeyer, M. I., Cid, L. P., Barros, L. F., & Sepulveda, F. V. (2001). Modulation of the two-pore domain acid-sensitive K+ channel TASK-2 (KCNK5) by changes in cell volume. Journal of Biological Chemistry, 276, 43166–43174.

    PubMed  CAS  Google Scholar 

  158. Niemeyer, M. I., Cid, L. P., Valenzuela, X., Paeile, V., & Sepulveda, F. V. (2003). Extracellular conserved cysteine forms an intersubunit disulphide bridge in the KNCK5 (TASK-2) K+ channels without having an essential effect upon activity. Molecular Membrane Biology, 20, 185–191.

    PubMed  CAS  Google Scholar 

  159. Niu, W., & Sachs, F. (2003). Dynamic properties of stretch-activated K+ channels in adult rat atrial myocytes. Progress in Biophysics and Molecular Biology, 82, 121–135.

    PubMed  CAS  Google Scholar 

  160. O’Connell, A. D., Morton, M. J., & Hunter, M. (2002). Two-pore domain K+ channels-molecular sensors. Biochimica Biophysica Acta, 1566, 152–161.

    CAS  Google Scholar 

  161. O’Kelly, I., Butler, M. H., Zilberberg, N., & Goldstein, S. A. N. (2002). Forward transport: 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell, 111, 577–588.

    PubMed  CAS  Google Scholar 

  162. Orias, M., Velazquez, H., Tung, F., Lee, G., & Desir, G. V. (1997). Cloning and localization of a double-pore K channel, KCNK1: Exclusive expression in distal nephron segments. American Journal of Physiology. Renal Physiology, 273, F663–F666.

    CAS  Google Scholar 

  163. Ozaita, A., & Vega-Saenz de Miera, E. (2002). Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+ channel gene KCNK4: Chromosomal localization, tissue distribution and functional expression. Molecular Brain Research, 102, 18–27.

    PubMed  CAS  Google Scholar 

  164. Park, K. J., Baker, S. A., Cho, S. Y., Sanders, K. M., & Koh, S. D. (2005). Sulfur-containing amino acids block stretch-dependent K+ channels and nitrergic responses in the murine colon. British Journal of Pharmacology, 144, 1126–1137.

    PubMed  CAS  Google Scholar 

  165. Patel, A. J., & Honoré, E. (2001). Anesthetic-sensitive 2P domain K+ channels. Anesthesiology, 95, 1013–1021.

    PubMed  CAS  Google Scholar 

  166. Patel, A. J., Honoré, E., Lesage, F., Fink, M., Romey, G., & Lazdunski, M. (1999). Inhalation anesthetics activate two-pore domain background K+ channels. Nature Neuroscience, 2, 422–426.

    PubMed  CAS  Google Scholar 

  167. Patel, A. J., Honoré, E., Maingret, F., Lesage, F., Fink, M., Duprat, F., & Lazdunski, M. (1998). A mammalian two pore domain mechano-gated S-like K+ channel. EMBO Journal, 17, 4283–4290.

    PubMed  CAS  Google Scholar 

  168. Patel, A. J., & Lazdunski, M. (2004). The 2P-domain K+ channels role in apoptosis and tumorigenesis. Pflügers Archiv, 448, 261–273.

    PubMed  CAS  Google Scholar 

  169. Patel, A. J., Lazdunski, M., & Honoré, E. (2001). Lipid and mechano-gated 2P domain K+ channels. Current Opinion in Cell Biology, 13, 422–428.

    PubMed  CAS  Google Scholar 

  170. Patel, A. J., Maingret, F., Magnone, V., Fosset, M., Lazdunski, M., & Honoré, E. (2000). TWIK-2, an inactivating 2P domain K+ channel. Journal of Biological Chemistry, 275, 28722–28730.

    PubMed  CAS  Google Scholar 

  171. Plant, L. D., Kemp, P. J., Peers, C., Henderson, Z., & Pearson, H. A. (2002). Hypoxic depolarization of cerebellar granule neurons by specific inhibition of TASK-1. Stroke, 33, 2324–2328.

    PubMed  Google Scholar 

  172. Plant, L. D., Rajan, S., & Goldstein, S. A. N. (2005). K2P channels and their protein partners. Current Opinion in Neurobiology, 15, 326–333.

    PubMed  CAS  Google Scholar 

  173. Pountney, D. J., Gulkarov, I., Vega-Saenz de Miera, E., Holmes, D., Saganich, M., Rudy, B., Artman, M., & Coetzee, W. A. (1999). Identification and cloning of TWIK-originated similarity sequence (TOSS): A novel human 2-pore K+ channel principle subunit. FEBS Letters, 450, 191–196.

    PubMed  CAS  Google Scholar 

  174. Punke, M. A., Licher, T., Pongs, O., & Friederich, P. (2003). Inhibition of human TREK-1 channels by bupivacaine. Anesthesia and Analgesia, 96, 1665–1673.

    PubMed  CAS  Google Scholar 

  175. Rajan, S., Plant, L. D., Rabin, M. L., Butler, M. H., & Goldstein, S. A. N. (2005). Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell, 121, 37–47.

    PubMed  CAS  Google Scholar 

  176. Rajan, S., Preisig-Muller, R., & Wischmeyer, E., et al. (2002). Interaction with 14–3–3 proteins remotes functional expression of the potassium channels TASK-1 and TASK-3. The Journal of Physiology, 545, 13–26.

    PubMed  CAS  Google Scholar 

  177. Rajan, S., Wischmeyer, E., Karschin, C., Preisig-Müller, R., Grzeschik, K.-H., Daut, J., Karschin, A., & Derst, C. (2001). THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels. Journal of Biological Chemistry, 276, 7302–7311.

    PubMed  CAS  Google Scholar 

  178. Rajan, S., Wischmeyer, E., Liu, G.-X., Presig-Muller, R., Daut, J., Karschin, A., & Derst, C. (2000). TASK-3, a novel tandem pore domain acid-sensitive K+ channel. Journal of Biological Chemistry, 275, 16650–16657.

    PubMed  CAS  Google Scholar 

  179. Reid, J. D., Lukas, W., Shafaatian, R., Bertl, A., Scheurmannkettner, C., Guy, H. R., & North, R. A. (1996). The S. cerevisiae outwardly-rectifying potassium channel (DUK1) identifies a new family of channels with duplicated pore domains. Receptors Channels, 4, 51–62.

    PubMed  CAS  Google Scholar 

  180. Renigunta, V., Yuan, H. B., Zuzarte, M., Rinne, S., Koch, A., Wischmeyer, E., Schlichthorl, G., Gao, Y. D., Karschin, A., Jacob, R., Schwappach, B., Daut, J., & Preisig-Muller, R. (2006). The retention factor p11 confers an endoplasmic reticulum-localization signal to the potassium channel TASK-1. Traffic, 7, 168–181.

    PubMed  CAS  Google Scholar 

  181. Reyes, R., Duprat, F., Lesage, F., Fink, M., Salinas, M., Farman, N., & Lazdunski, M. (1998). Cloning and expression of a novel pH-sensitive two-pore domain K+ channel from human kidney. Journal of Biological Chemistry, 273, 30863–30869.

    PubMed  CAS  Google Scholar 

  182. Richter, T. A., Dvoryanchikov, G. A., Chaudhari, N., & Roper, S. D. (2004). Acid-sensitive two-pore domain potassium (K2P) channels in mouse taste buds. Journal of Neurophysiology, 92, 1928–1936.

    PubMed  CAS  Google Scholar 

  183. Salinas, M., Reyes, R., Lesage, F., Fossett, M., Heurteaux, C., Romey, G., & Lazdunski, M. (1999). Cloning of a new mouse two-P domain channel subunit and a human homologue with a unique pore structure. Journal of Biological Chemistry, 274, 11751–11760.

    PubMed  CAS  Google Scholar 

  184. Sanders, K. M., & Koh, S. D. (2006). Two-pore-domain potassium channels in smooth muscles: New components of myogenic regulation. The Journal of Physiology, 570, 37–43.

    PubMed  CAS  Google Scholar 

  185. Sano, Y., Inamrua, K., Miyake, A., Mochizuki, S., Kitada, C., Yokoi, H., Nozawa, K., Okada, H., Matsushime, H., & Furuichi, K. (2003). A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord. Journal of Biological Chemistry, 278, 27406–27412.

    PubMed  CAS  Google Scholar 

  186. Sirois, J. E., Lei, Q., Talley, E. M., Lynch, C. III, & Bayliss, D. A. (2000). The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics. Journal of Neuroscience, 20, 6347–6354.

    PubMed  CAS  Google Scholar 

  187. Sirois, J. E., Lynch III, C., & Bayliss, D. A. (2002). Convergent and reciprocal modulation of a leak K+ current and Ih by and inhalational anaesthetic and neurotransmitters in rat brainstem motoneurons. The Journal of Physiology, 541, 717–729.

    PubMed  CAS  Google Scholar 

  188. Skatchkov, S. N., Eaton, M. J., Shuba, Y. M., Kucheryavykh, Y. V., Derst, C., Veh, R. W., Wurm, A., Iandiev, I., Pannicke, T., Bringmann, A., & Reichenbach, A. (2006). Tandem-pore domain potassium channels are functionally expressed in retinal (Müller) glial cells. Glia, 53, 266–276.

    PubMed  CAS  Google Scholar 

  189. Suh, B.-C., & Hille, B. (2005). Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate. Current Opinion in Neurobiology, 15, 370–378.

    PubMed  CAS  Google Scholar 

  190. Szabadkai, G., Varnai, P., & Enyedi, P. (1999). Selective inhibition of potassium-stimulated rat adrenal glomerulosa cells by ruthenium red. Biochemical Pharmacology, 57, 209–218.

    PubMed  CAS  Google Scholar 

  191. Takahira, M., Sakurai, M., Sakurada, N., & Sugiyama, K. (2005). Fenamates and diltiazem modulate lipid-sensitive mechano-gated 2P domain K+ channels. Pflügers Archiv, 451, 474–478.

    PubMed  CAS  Google Scholar 

  192. Talley, E. M., & Bayliss, D. A. (2002). Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: Volatile anesthetics and neurotransmitters share a molecular site of action. Journal of Biological Chemistry, 277, 17733–17742.

    PubMed  CAS  Google Scholar 

  193. Talley, E. M., Lei, Q., Sirois, J. E., & Bayliss, D. A. (2000). TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. Neuron, 25, 399–410.

    PubMed  CAS  Google Scholar 

  194. Talley, E. M., Solorzano, G., Lei, Q., Kim, D., & Bayliss, D. A. (2001). CNS distribution of members of the two-pore-domain (KCNK) potassium channel family. The Journal of Neuroscience, 21, 7491–7505.

    PubMed  CAS  Google Scholar 

  195. Tan, J. H. C., Liu, W., & Saint, D. A. (2002). Trek-like potassium channels in rat cardiac ventricular myocytes are activated by intracellular ATP. Journal of Membrane Biology, 185, 201–207.

    PubMed  CAS  Google Scholar 

  196. Taverna, S., Tkatch, T., Metz, A. E., & Martina, M. (2005). Differential expression of TASK channels between horizontal interneurons and pyramidal cells of rat hippocampus. Journal of Neuroscience, 25, 9162–9170.

    PubMed  CAS  Google Scholar 

  197. Terrenoire, C., Lauritzen, I., Lesage, F., Romey, G., & Lazdunski, M. (2001). A TREK-1-like potassium channel in atrial cells inhibited by β-adrenergic stimulation and activated by volatile anesthetics. Circulation Research, 89, 336–342.

    PubMed  CAS  Google Scholar 

  198. Torborg, C. L., Berg, A. P., Jeffries, B. W., Bayliss, D. A., & McBain, C. J. (2006). TASK-like conductances are present within hippocampal CA1 stratum oriens interneuron subpopluations. Journal of Neuroscience, 26, 7362–7367.

    PubMed  CAS  Google Scholar 

  199. Vega-Saenz de Miera, E., Lau, D. H. P., Zhadina, M., Pountney, D., Coetzee, W. A., & Rudy, B. (2001). KT3.2 and KT3.3, two novel human two pore K+ channels closely related to TASK-1. Journal of Neurophysiology, 86, 130–142.

    PubMed  CAS  Google Scholar 

  200. Warth, R., Barriere, H., Meneton, P., Bloch, M., Thomas, J., Tauc, M., Heitzmann, D., Romeo, E., Verrey, F., Mengual, R., Guy, N., Bendahhou, S., Lesage Fm Poujeal, P., & Barhanin, J. (2004). Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport. Proceedings of the National Academy of Sciences of the United States of America, 101, 8215–8220.

    PubMed  CAS  Google Scholar 

  201. Washburn, C. P., Sirois, J. E., Talley, E. M., Guyenet, P. G., & Bayliss, D. A. (2002). Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance. Journal of Neuroscience, 22, 1256–1265.

    PubMed  CAS  Google Scholar 

  202. Watkins, C. S., & Mathie, A. (1996). A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons. The Journal of Physiology, 491, 401–412.

    PubMed  CAS  Google Scholar 

  203. Williams, B. A., & Buckler, K. J. (2004). Biophysical properties and metabolic regulation of a TASK-like potassium channel in rat carotid body type 1 cells. American Journal of Physiology. Lung Cellular and Molecular Physiology, 286, L221–L230.

    PubMed  CAS  Google Scholar 

  204. Wyatt, C. N., & Buckler, K. J. (2004). The effects of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type 1 cells. The Journal of Physiology, 556, 175–191.

    PubMed  CAS  Google Scholar 

  205. Xu, L., & Enyeart, J. J. (2001). Properties of ATP-dependent K+ channels in adrenocortical cells. American Journal of Physiology. Cell Physiology, 280, C199–C215.

    PubMed  CAS  Google Scholar 

  206. Yamamoto, Y., Kummer, W., Atoji, Y., & Suzuki, Y. (2002). TASK-1, TASK-2, TASK-3 and TRAAK immunoreactivities in the rat carotid body. Brain Research, 950, 304–307.

    PubMed  CAS  Google Scholar 

  207. Yamamoto, Y., & Taniguchi, K. (2006). Expression of tandem P domain K+ channel, TREK-1, in the rat carotid body. The Journal of Histochemistry and Cytochemistry, 54, 467–472.

    PubMed  CAS  Google Scholar 

  208. Zanzouri, M., Lauritzen, I., Duprat, F., Mazzuca, M., Lesage, F., & Lazdunski, M. (2006). Membrane potential-regulated transcription of the resting K+ conductance TASK-3 via the calcineurin pathway. Journal of Biological Chemistry, 281, 28910–28918.

    PubMed  CAS  Google Scholar 

  209. Zhou, X. L., Vaillant, B., Loukin, S. H., & Saimi, Y. (1995). YKC1 encodes the depolarization-activated K+ channel in the plasma membrane of yeast. FEBS Letters, 373, 170–176.

    PubMed  CAS  Google Scholar 

  210. Zilberberg, N., Ilan, N., & Goldstein, S. A. N. (2001). KCNKø: Opening and closing the 2-P-domain potassium leak channels entails “C-type” gating of the outer pore. Neuron, 32, 635–648.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I would especially like to thank Péter Enyedi for his helpful discussion of their receptor-mediated channel modulation experiments and Douglas Bayliss for sharing his insights and unpublished data on cloned rTASK channel Zn2+ sensitivity. I would also like to thank the reviewers for their constructive criticisms and insights to the literature of this rapidly expanding field.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Northern Illinois University, DeKalb, IL, 60115, USA

    David P. Lotshaw

Authors
  1. David P. Lotshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David P. Lotshaw.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lotshaw, D.P. Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels. Cell Biochem Biophys 47, 209–256 (2007). https://doi.org/10.1007/s12013-007-0007-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-007-0007-8

Keywords

Search

Navigation