Abstract
A key feature of potassium channel function is the ability to switch between conducting and non-conducting states by undergoing conformational changes in response to cellular or extracellular signals. Such switching is facilitated by the mechanical coupling of gating domain movements to pore opening and closing. Two-pore domain potassium channels (K2P) conduct leak or background potassium-selective currents that are mostly time- and voltage-independent. These channels play a significant role in setting the cell resting membrane potential and, therefore modulate cell responsiveness and excitability. Thus, K2P channels are key players in numerous physiological processes and were recently shown to also be involved in human pathologies. It is well established that K2P channel conductance, open probability and cell surface expression are significantly modulated by various physical and chemical stimuli. However, in understanding how such signals are translated into conformational changes that open or close the channels gate, there remain more open questions than answers. A growing line of evidence suggests that the outer pore area assumes a critical role in gating K2P channels, in a manner reminiscent of C-type inactivation of voltage-gated potassium channels. In some K2P channels, this gating mechanism is facilitated in response to external pH levels. Recently, it was suggested that K2P channels also possess a lower activation gate that is positively coupled to the outer pore gate. The purpose of this review is to present an up-to-date summary of research describing the conformational changes and gating events that take place at the K2P channel ion-conducting pathway during the channel regulation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alloui A, Zimmermann K, Mamet J, Duprat F, 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 J 25:2368–2376. doi:10.1038/sj.emboj.7601116
Armstrong CM (2003) Voltage-gated K channels. Sci STKE 2003:re10. doi:10.1126/stke.2003.188.re10
Backx PH, Marban E (1993) Background potassium current active during the plateau of the action potential in guinea pig ventricular myocytes. Circ Res 72:890–900
Barel O, Shalev SA, Ofir R, Cohen A, Zlotogora J, Shorer Z, Mazor G, Finer G, Khateeb S, Zilberberg N, Birk OS (2008) Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9. Am J Hum Genet 83:193–199. doi:10.1016/j.ajhg.2008.07.010
Baukrowitz T, Yellen G (1995) Modulation of K+ current by frequency and external K+: a tale of two inactivation mechanisms. Neuron 15:951–960. doi:10.1016/0896-6273(95)90185-X
Baukrowitz T, Yellen G (1996) Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel. Science 271:653–656. doi:10.1126/science.271.5249.653
Ben-Abu Y, Zhou Y, Zilberberg N, Yifrach O (2009) Inverse coupling in leak and voltage-activated K+ channel gates underlies distinct roles in electrical signaling. Nat Struct Mol Biol 16:71–79. doi:10.1038/nsmb.1525
Bezanilla F, Armstrong CM (1972) Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons. J Gen Physiol 60:588–608. doi:10.1085/jgp.60.5.588
Bockenhauer D, Zilberberg N, Goldstein SA (2001) KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nat Neurosci 4:486–491
Brickley SG, Aller MI, Sandu C, Veale EL, Alder FG, Sambi H, Mathie A, Wisden W (2007) TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons. J Neurosci 27:9329–9340. doi:10.1523/JNEUROSCI.1427-07.2007
Buckler KJ, Williams BA, Honore E (2000) An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. J Physiol 525:135–142. doi:10.1111/j.1469-7793.2000.00135.x
Chemin J, Patel AJ, Duprat F, Lauritzen I, Lazdunski M, Honore E (2005) A phospholipid sensor controls mechanogating of the K+ channel TREK-1. EMBO J 24:44–53. doi:10.1038/sj.emboj.7600494
Chemin J, Patel AJ, Duprat F, Sachs F, Lazdunski M, Honore E (2007) Up- and down-regulation of the mechano-gated K2P channel TREK-1 by PIP2 and other membrane phospholipids. Pflugers Arch 455:97–103. doi:10.1007/s00424-007-0250-2
Chen X, Talley EM, Patel N, Gomis A, McIntire WE, Dong B, Viana F, Garrison JC, Bayliss DA (2006) Inhibition of a background potassium channel by Gq protein alpha-subunits. Proc Natl Acad Sci USA 103:3422–3427. doi:10.1073/pnas.0507710103
Chesler M (2003) Regulation and modulation of pH in the brain. Physiol Rev 83:1183–1221
Choe S (2002) Potassium channel structures. Nat Rev Neurosci 3:115–121. doi:10.1038/nrn727
Choi KL, Aldrich RW, Yellen G (1991) Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels. Proc Natl Acad Sci USA 88:5092–5095. doi:10.1073/pnas.88.12.5092
Clarke CE, Veale EL, Green PJ, Meadows HJ, Mathie A (2004) Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc. J Physiol 560:51–62. doi:10.1113/jphysiol.2004.070292
Clarke CE, Hill AP, Zhao J, Kondo M, Subbiah RN, Campbell TJ, Vandenberg JI (2006) Effect of S5P alpha-helix charge mutants on inactivation of hERG K+ channels. J Physiol 573:291–304. doi:10.1113/jphysiol.2006.108332
Clarke CE, Veale EL, Wyse K, Vandenberg JI, Mathie A (2008) The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function. J Biol Chem 283:16985–16992. doi:10.1074/jbc.M801368200
Claydon TW, Makary SY, Dibb KM, Boyett MR (2004) K+ activation of Kir3.1/Kir3.4 and Kv1.4 K+ channels is regulated by extracellular charges. Biophys J 87:2407–2418. doi:10.1529/biophysj.103.039073
Cohen A, Zilberberg N (2006) Fluctuations in Xenopus oocytes protein phosphorylation levels during two-electrode voltage clamp measurements. J Neurosci Methods 153:62–70. doi:10.1016/j.jneumeth.2005.10.005
Cohen A, Ben-Abu Y, Hen S, Zilberberg N (2008) A novel mechanism for human K2P2.1 channel gating: facilitation of C-type gating by protonation of extracellular histidine residues. J Biol Chem 283:19448–19455. doi:10.1074/jbc.M801273200
Cohen A, Sagron R, Somech E, Segal-Hayoun Y, Zilberberg N (2009) Pain-associated signals, acidosis and lysophosphatidic acid, modulate the neuronal K2P2.1 channel. Mol Cell Neurosci 40:382–389. doi:10.1016/j.mcn.2008.12.004
Cordero-Morales JF, Cuello LG, Zhao Y, Jogini V, Cortes DM, Roux B, Perozo E (2006) Molecular determinants of gating at the potassium-channel selectivity filter. Nat Struct Mol Biol 13:311–318. doi:10.1038/nsmb1069
Cordero-Morales JF, Jogini V, Lewis A, Vasquez V, Cortes DM, Roux B, Perozo E (2007) Molecular driving forces determining potassium channel slow inactivation. Nat Struct Mol Biol 14:1062–1069. doi:10.1038/nsmb1309
Dedman A, Sharif-Naeini R, Folgering JH, Duprat F, Patel A, Honore E (2009) The mechano-gated K(2P) channel TREK-1. Eur Biophys J 38:293–303. doi:10.1007/s00249-008-0318-8
Deitmer JW, Rose CR (1996) pH regulation and proton signalling by glial cells. Prog Neurobiol 48:73–103. doi:10.1016/0301-0082(95)00039-9
Doring F, Scholz H, Kuhnlein RP, Karschin A, Wischmeyer E (2006) Novel Drosophila two-pore domain K channels: rescue of channel function by heteromeric assembly. Eur J Neurosci 24:2264–2274. doi:10.1111/j.1460-9568.2006.05102.x
Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77. doi:10.1126/science.280.5360.69
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 J 16:5464–5471. doi:10.1093/emboj/16.17.5464
Duprat F, Lesage F, Patel AJ, Fink M, Romey G, Lazdunski M (2000) The neuroprotective agent riluzole activates the two P domain K+ channels TREK-1 and TRAAK. Mol Pharmacol 57:906–912
Eduljee C, Claydon TW, Viswanathan V, Fedida D, Kehl SJ (2007) SCAM analysis reveals a discrete region of the pore turret that modulates slow inactivation in Kv1.5. Am J Physiol Cell Physiol 292:C1041–C1052. doi:10.1152/ajpcell.00274.2006
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 J 15:6854–6862
Franks NP, Honore E (2004) The TREK K2P channels and their role in general anaesthesia and neuroprotection. Trends Pharmacol Sci 25:601–608. doi:10.1016/j.tips.2004.09.003
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. Biochem Biophys Res Commun 282:249–256. doi:10.1006/bbrc.2001.4562
Goldstein SA, Bockenhauer D, O’Kelly I, Zilberberg N (2001) Potassium leak channels and the KCNK family of two-P-domain subunits. Nat Rev Neurosci 2:175–184. doi:10.1038/35058574
Grissmer S, Cahalan M (1989) TEA prevents inactivation while blocking open K+ channels in human T lymphocytes. Biophys J 55:203–206. doi:10.1016/S0006-3495(89)82793-6
Gurney A, Manoury B (2009) Two-pore potassium channels in the cardiovascular system. Eur Biophys J 38:305–318. doi:10.1007/s00249-008-0326-8
Han J, Kang D, Kim D (2003) Functional properties of four splice variants of a human pancreatic tandem-pore K+ channel, TALK-1. Am J Physiol Cell Physiol 285:C529–C538
Heurteaux C, Lucas G, Guy N, El Yacoubi M, Thummler S, Peng XD, Noble F, Blondeau N, Widmann C, Borsotto M, Gobbi G, Vaugeois JM, Debonnel G, Lazdunski M (2006) Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat Neurosci 9:1134–1141. doi:10.1038/nn1749
Hille B (2001) Ion channels of excitable membranes, 3rd edn. Sinauer Associates Press, Sanderland
Honore E (2007) The neuronal background K2P channels: focus on TREK1. Nat Rev Neurosci 8:251–261. doi:10.1038/nrn2117
Honore E, Maingret F, Lazdunski M, Patel AJ (2002) An intracellular proton sensor commands lipid- and mechano-gating of the K+ channel TREK-1. EMBO J 21:2968–2976. doi:10.1093/emboj/cdf288
Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (2002) The open pore conformation of potassium channels. Nature 417:523–526. doi:10.1038/417523a
Kang D, Kim D (2004) Single-channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family. Biochem Biophys Res Commun 315:836–844. doi:10.1016/j.bbrc.2004.01.137
Kang D, Choe C, Cavanaugh E, Kim D (2007) Properties of single two-pore domain TREK-2 channels expressed in mammalian cells. J Physiol 583:57–69. doi:10.1113/jphysiol.2007.136150
Kehl SJ, Eduljee C, Kwan DC, Zhang S, Fedida D (2002) Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn(2+). J Physiol 541:9–24. doi:10.1113/jphysiol.2001.014456
Kim Y, Bang H, Kim D (2000) TASK-3, a new member of the tandem pore K+ channel family. J Biol Chem 275:9340–9347. doi:10.1074/jbc.275.13.9340
Kim Y, Bang H, Gnatenco C, Kim D (2001) Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali. Pflugers Arch 442:64–72. doi:10.1007/s004240000496
Kurata HT, Fedida D (2006) A structural interpretation of voltage-gated potassium channel inactivation. Prog Biophys Mol Biol 92:185–208. doi:10.1016/j.pbiomolbio.2005.10.001
Lalevee N, Monier B, Senatore S, Perrin L, Semeriva M (2006) Control of cardiac rhythm by ORK1, a Drosophila two-pore domain potassium channel. Curr Biol 16:1502–1508. doi:10.1016/j.cub.2006.05.064
Larsson HP, Elinder F (2000) A conserved glutamate is important for slow inactivation in K+ channels. Neuron 27:573–583. doi:10.1016/S0896-6273(00)00067-2
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. J Biol Chem 275:28398–28405. doi:10.1074/jbc.M002822200
Liu J, Zhang M, Jiang M, Tseng GN (2002) Structural and functional role of the extracellular s5-p linker in the HERG potassium channel. J Gen Physiol 120:723–737. doi:10.1085/jgp.20028687
Long SB, Campbell EB, Mackinnon R (2005) Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309:897–903. doi:10.1126/science.1116269
Lopes CM, Gallagher PG, Buck ME, Butler MH, Goldstein SA (2000) Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J Biol Chem 275:16969–16978. doi:10.1074/jbc.M001948200
Lopes CM, Zilberberg N, Goldstein SA (2001) Block of Kcnk3 by protons. Evidence that 2-P-domain potassium channel subunits function as homodimers. J Biol Chem 276:24449–24452. doi:10.1074/jbc.C100184200
Lopes CM, Rohacs T, Czirjak G, Balla T, Enyedi P, Logothetis DE (2005) PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels. J Physiol 564:117–129. doi:10.1113/jphysiol.2004.081935
Lopes CM, Remon JI, Matavel A, Sui JL, Keselman I, Medei E, Shen Y, Rosenhouse-Dantsker A, Rohacs T, Logothetis DE (2007) Protein kinase A modulates PLC-dependent regulation and PIP2-sensitivity of K+ channels. Channels Austin 1:124–134
Lopez-Barneo J, Hoshi T, Heinemann SH, Aldrich RW (1993) Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels. Receptors Channels 1:61–71
Lotshaw DP (2006) Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells. J Membr Biol 210:51–70. doi:10.1007/s00232-005-7012-x
Magidovich E, Yifrach O (2004) Conserved gating hinge in ligand- and voltage-dependent K+ channels. Biochemistry 43:13242–13247. doi:10.1021/bi048377v
Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (1999) Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274:26691–26696. doi:10.1074/jbc.274.38.26691
Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, Lazdunski M, Honore E (2000a) TREK-1 is a heat-activated background K+ channel. EMBO J 19:2483–2491. doi:10.1093/emboj/19.11.2483
Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (2000b) Lysophospholipids open the two-pore domain mechano-gated K+ channels TREK-1 and TRAAK. J Biol Chem 275:10128–10133. doi:10.1074/jbc.275.14.10128
Mathie A (2007) Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors. J Physiol 578:377–385. doi:10.1113/jphysiol.2006.121582
Meuth SG, Budde T, Kanyshkova T, Broicher T, Munsch T, Pape HC (2003) Contribution of TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 channels to the control of activity modes in thalamocortical neurons. J Neurosci 23:6460–6469
Morton MJ, O’Connell AD, Sivaprasadarao A, Hunter M (2003) Determinants of pH sensing in the two-pore domain K(+) channels TASK-1 and -2. Pflugers Arch 445:577–583
Morton MJ, Abohamed A, Sivaprasadarao A, Hunter M (2005) pH sensing in the two-pore domain K+ channel, TASK2. Proc Natl Acad Sci USA 102:16102–16106. doi:10.1073/pnas.0506870102
Mu D, Chen L, Zhang X, See LH, Koch CM, Yen C, Tong JJ, Spiegel L, Nguyen KC, Servoss A, Peng Y, Pei L, Marks JR, Lowe S, Hoey T, Jan LY, McCombie WR, Wigler MH, Powers S (2003) Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. Cancer Cell 3:297–302. doi:10.1016/S1535-6108(03)00054-0
Murbartian J, Lei Q, Sando JJ, Bayliss DA (2005) Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. J Biol Chem 280:30175–30184. doi:10.1074/jbc.M503862200
Niemeyer M, González-Nilo F, Zúñiga L, González W, Cid L, Sepúlveda F (2007) Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel. Proc Natl Acad Sci USA 104:666–671. doi:10.1073/pnas.0606173104
O’Connell AD, Morton MJ, Sivaprasadarao A, Hunter M (2005) Selectivity and interactions of Ba2+ and Cs+ with wild-type and mutant TASK1 K+ channels expressed in Xenopus oocytes. J Physiol 562:687–696. doi:10.1113/jphysiol.2004.079020
Ogielska EM, Aldrich RW (1999) Functional consequences of a decreased potassium affinity in a potassium channel pore. Ion interactions and C-type inactivation. J Gen Physiol 113:347–358. doi:10.1085/jgp.113.2.347
Ortega-Saenz P, Pardal R, Castellano A, Lopez-Barneo J (2000) Collapse of conductance is prevented by a glutamate residue conserved in voltage-dependent K+ channels. J Gen Physiol 116:181–190. doi:10.1085/jgp.116.2.181
Panyi G, Deutsch C (2006) Cross talk between activation and slow inactivation gates of Shaker potassium channels. J Gen Physiol 128:547–559. doi:10.1085/jgp.200609644
Panyi G, Deutsch C (2007) Probing the cavity of the slow inactivated conformation of Shaker potassium channels. J Gen Physiol 129:403–418. doi:10.1085/jgp.200709758
Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M (1999) Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci 2:422–426. doi:10.1038/8084
Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honore E (2000) TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem 275:28722–28730. doi:10.1074/jbc.M003755200
Pei L, Wiser O, Slavin A, Mu D, Powers S, Jan LY, Hoey T (2003) Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function. Proc Natl Acad Sci USA 100:7803–7807. doi:10.1073/pnas.1232448100
Rajan S, Wischmeyer E, Xin Liu G, Preisig-Muller R, Daut J, Karschin A, Derst C (2000) TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histiding as pH sensor. J Biol Chem 275:16650–16657. doi:10.1074/jbc.M000030200
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. J Biol Chem 273:30863–30869. doi:10.1074/jbc.273.47.30863
Simkin D, Cavanaugh EJ, Kim D (2008) Control of the single channel conductance of K2P10.1 (TREK-2) by the amino-terminus: role of alternative translation initiation. J Physiol 586:5651–5663. doi:10.1113/jphysiol.2008.161927
Stansfeld PJ, Grottesi A, Sands ZA, Sansom MS, Gedeck P, Gosling M, Cox B, Stanfield PR, Mitcheson JS, Sutcliffe MJ (2008) Insight into the mechanism of inactivation and pH sensitivity in potassium channels from molecular dynamics simulations. Biochemistry 47:7414–7422. doi:10.1021/bi800475j
Starkus JG, Kuschel L, Rayner MD, Heinemann SH (1997) Ion conduction through C-type inactivated Shaker channels. J Gen Physiol 110:539–550. doi:10.1085/jgp.110.5.539
Starkus JG, Varga Z, Schonherr R, Heinemann SH (2003) Mechanisms of the inhibition of Shaker potassium channels by protons. Pflugers Arch 447:44–54. doi:10.1007/s00424-003-1121-0
Talley EM, Lei Q, Sirois JE, Bayliss DA (2000) TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. Neuron 25:399–410. doi:10.1016/S0896-6273(00)80903-4
Thomas D, Plant LD, Wilkens CM, McCrossan ZA, Goldstein SA (2008) Alternative translation initiation in rat brain yields K(2P)2.1 potassium channels permeable to sodium. Neuron 58:859–870. doi:10.1016/j.neuron.2008.04.016
Torres AM, Bansal PS, Sunde M, Clarke CE, Bursill JA, Smith DJ, Bauskin A, Breit SN, Campbell TJ, Alewood PF, Kuchel PW, Vandenberg JI (2003) Structure of the HERG K+ channel S5P extracellular linker: role of an amphipathic alpha-helix in C-type inactivation. J Biol Chem 278:42136–42148. doi:10.1074/jbc.M212824200
Veale EL, Kennard LE, Sutton GL, MacKenzie G, Sandu C, Mathie A (2007) G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C. Mol Pharmacol 71:1666–1675. doi:10.1124/mol.106.033241
Voloshyna I, Besana A, Castillo M, Matos T, Weinstein IB, Mansukhani M, Robinson RB, Cordon-Cardo C, Feinmark SJ (2008) TREK-1 is a novel molecular target in prostate cancer. Cancer Res 68:1197–1203. doi:10.1158/0008-5472.CAN-07-5163
Wagner PG, Dekin MS (1997) cAMP modulates an S-type K+ channel coupled to GABAB receptors in mammalian respiratory neurons. Neuroreport 8:1667–1670. doi:10.1097/00001756-199705060-00021
Yellen G, Sodickson D, Chen TY, Jurman ME (1994) An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding. Biophys J 66:1068–1075. doi:10.1016/S0006-3495(94)80888-4
Yifrach O, MacKinnon R (2002) Energetics of pore opening in a voltage-gated K+ channel. Cell 111:231–239. doi:10.1016/S0092-8674(02)01013-9
Yuill K, Ashmole I, Stanfield PR (2004) The selectivity filter of the tandem pore potassium channel TASK-1 and its pH sensitivity and ionic selectivity. Pflugers Arch 448:63–69. doi:10.1007/s00424-003-1218-5
Yuill KH, Stansfeld PJ, Ashmole I, Sutcliffe MJ, Stanfield PR (2007) The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1: contributions of the pore domains. Pflugers Arch 455:333–348. doi:10.1007/s00424-007-0282-7
Zilberberg N, Ilan N, Gonzalez-Colaso R, Goldstein SA (2000) Opening and closing of KCNKO potassium leak channels is tightly regulated. J Gen Physiol 116:721–734. doi:10.1085/jgp.116.5.721
Zilberberg N, Ilan N, Goldstein SA (2001) KCNKO: opening and closing the 2-P-domain potassium leak channel entails “C-type” gating of the outer pore. Neuron 32:635–648. doi:10.1016/S0896-6273(01)00503-7
Acknowledgments
This research was funded by grants from the Binational (US-Israel) Science Foundation (grant 2005112), the Israel Science Foundation (grant 431/03) and the Zlotowski Center for Neuroscience. We thank D. Dotan-Cohen for graphic assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
“Proteins, membranes and cells: the structure–function nexus”. Contributions from the annual scientific meeting (including a special symposium in honour of Professor Alex Hope of Flinders University, South Australia) of the Australian Society for Biophysics held in Canberra, ACT, Australia, September 28 to October 1, 2008.
Rights and permissions
About this article
Cite this article
Cohen, A., Ben-Abu, Y. & Zilberberg, N. Gating the pore of potassium leak channels. Eur Biophys J 39, 61–73 (2009). https://doi.org/10.1007/s00249-009-0457-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00249-009-0457-6