An unexpected role for TASK-3 potassium channels in network oscillations with implications for sleep mechanisms and anesthetic action
Open accessAbstract
TASK channels are acid-sensitive and anesthetic-activated members of the family of two-pore-domain potassium channels. We have made the surprising discovery that the genetic ablation of TASK-3 channels eliminates a specific type of theta oscillation in the cortical electroencephalogram (EEG) resembling type II theta (4–9 Hz), which is thought to be important in processing sensory stimuli before initiating motor activity. In contrast, ablation of TASK-1 channels has no effect on theta oscillations. Despite the absence of type II theta oscillations in the TASK-3 knockout (KO) mice, the related type I theta, which has certain neuronal pathways in common and is involved in exploratory behavior, is unaffected. In addition to the absence of type II theta oscillations, the TASK-3 KO animals show marked alterations in both anesthetic sensitivity and natural sleep behavior. Their sensitivity to halothane, a potent activator of TASK channels, is greatly reduced, whereas their sensitivity to cyclopropane, which does not activate TASK-3 channels, is unchanged. The TASK-3 KO animals exhibit a slower progression from their waking to sleeping states and, during their sleeping period, their sleep episodes as well as their REM theta oscillations are more fragmented. These results imply a previously unexpected role for TASK-3 channels in the cellular mechanisms underlying these behaviors and suggest that endogenous modulators of these channels may regulate theta oscillations.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Deletion of TASK-1 and TASK-3 in mice is linked to partial volatile anesthetic resistance; loss of TASK-3 reduces halothane sensitivity, stabilizes wakefulness, and slows transitions into sleep.
“Although deletion of TASK-1 and TASK-3 channels in mice is also associated with partial resistance to volatile anesthetics, the specific loss of TASK-3 not only reduces sensitivity to halothane, it also appears to stabilize the awake state and slows transitions into states of endogenous sleep [51, 52].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [52]
Cites
The wavelet transform, time-frequency localization and signal analysis
Daubechies, I. (1990) · IEEE Transactions on Information Theory · doi:10.1109/18.57199 · Cited by 6,483 · see citing works
Theta oscillations in the hippocampus
Buzsáki, G. (2002) · Neuron · doi:10.1016/s0896-6273(02)00586-x · Cited by 3,332 · see citing works
WAVELET TRANSFORMS AND THEIR APPLICATIONS TO TURBULENCE
Marie Farge, A. (1992) · Annual Review of Fluid Mechanics · doi:10.1146/annurev.fl.24.010192.002143 · Cited by 3,069 · see citing works
Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations
Klausberger, T., & Somogyi, P. (2008) · Science · doi:10.1126/science.1149381 · Cited by 2,050 · see citing works
Hippocampal electrical activity and voluntary movement in the rat
Vanderwolf, C. H. (1969) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(69)90092-3 · Cited by 1,928 · see citing works
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
Franks, N. P. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2372 · Cited by 1,266 · see citing works
Self-citationKramis, R., Vanderwolf, C. H., & Bland, B. H. (1975) · Experimental Neurology · doi:10.1016/0014-4886(75)90195-8 · Cited by 791 · see citing works
Molecular and neuronal substrates for general anaesthetics
Rudolph, U., & Antkowiak, B. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1496 · Cited by 771 · see citing works
Potassium leak channels and the KCNK family of two-p-domain subunits
Goldstein, S. A. N., Böckenhauer, D., O'Kelly, I., & Zilberberg, N. (2001) · Nature reviews. Neuroscience · doi:10.1038/35058574 · Cited by 721 · see citing works
(1997) · Neuroscience · doi:10.1016/s0306-4522(97)00239-x · Cited by 707 · see citing works
Inhalational anesthetics activate two-pore-domain background K+ channels
Patel, A. J., Honoré, E., Lesage, F., Fink, M., Romey, G., & Lazdunski, M. (1999) · Nature Neuroscience · doi:10.1038/8084 · Cited by 655 · see citing works
Emerging molecular mechanisms of general anesthetic action
Hemmings, H. C., Akabas, M. H., Goldstein, P. A., Trudell, J. R., Orser, B. A., & Harrison, N. L. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.08.006 · Cited by 542 · see citing works
TREK-1, a K+ channel involved in neuroprotection and general anesthesia
Heurteaux, C., Guy, N., Laigle, C., Blondeau, N., Duprat, F., Mazzuca, M., Lang‐Lazdunski, L., Widmann, C., Zanzouri, M., Romey, G., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600234 · Cited by 534 · see citing works
Wulff, P., Ponomarenko, A. A., Bartos, M., Korotkova, T. M., Fuchs, E. C., Bähner, F., Both, M., Tort, A. B. L., Kopell, N. J., Wisden, W., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813176106 · Cited by 400 · see citing works
Self-citationCellular mechanisms of neuronal population oscillations in the hippocampus in vitro
Traub, R. D., Bibbig, A., LeBeau, F. E. N., Buhl, E. H., & Whittington, M. A. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144303 · Cited by 358 · see citing works
General Anesthetics Hyperpolarize Neurons in the Vertebrate Central Nervous System
Nicoll, R. A., & Madison, D. V. (1982) · Science · doi:10.1126/science.7112112 · Cited by 312 · see citing works
Gruß, M., Bushell, T. J., Bright, D. P., Lieb, W. R., Mathie, A. A., & Franks, N. P. (2004) · Molecular Pharmacology · doi:10.1124/mol.65.2.443 · Cited by 309 · see citing works
Self-citationON BIOLOGICAL ASSAYS INVOLVING QUANTAL RESPONSES
Waud, D. R. (1972) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29374-0 · Cited by 247 · see citing works
Hippocampus, theta, and spatial memory
O'Keefe, J. M. (1993) · Current Opinion in Neurobiology · doi:10.1016/0959-4388(93)90163-s · Cited by 226 · see citing works
Grid cells and theta as oscillatory interference: Electrophysiological data from freely moving rats
Jeewajee, A., Barry, C., O'Keefe, J., & Burgess, N. (2008) · Hippocampus · doi:10.1002/hipo.20510 · Cited by 212 · see citing works
Kirk, I. J., & McNaughton, N. (1993) · Hippocampus · doi:10.1002/hipo.450030411 · Cited by 208 · see citing works
The frequency of rat's hippocampal theta rhythm is related to the speed of locomotion
Sławińska, U., & Kasicki, S. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00390-4 · Cited by 201 · see citing works
Volatile general anaesthetics activate a novel neuronal K+ current
Franks, N. P., & Lieb, W. R. (1988) · Nature · doi:10.1038/333662a0 · Cited by 199 · see citing works
Self-citationModulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) Potassium Channels
Talley, E. M., & Bayliss, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200502200 · Cited by 193 · see citing works
Rotstein, H. G., Pervouchine, D. D., Acker, C. D., Gillies, M. J., White, J. A., Buhl, E. H., Whittington, M. A., & Kopell, N. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00957.2004 · Cited by 175 · see citing works
Meuth, S. G., Budde, T., Kanyshkova, T. G., Broicher, T., Munsch, T., & Pape, H. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-16-06460.2003 · Cited by 170 · see citing works
Synchronization of Strongly Coupled Excitatory Neurons: Relating Network Behavior to Biophysics
Acker, C. D., Kopell, N., & White, J. A. (2003) · Journal of Computational Neuroscience · doi:10.1023/a:1024474819512 · Cited by 168 · see citing works
Rivas, J. L. M., Gaztelu, J. M., & Garc�a-Austt, E. (1996) · Experimental Brain Research · doi:10.1007/bf00242908 · Cited by 144 · see citing works
Hippocampal Formation Theta Activity and Movement Selection
Oddie, S. (1998) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(97)00003-1 · Cited by 140 · see citing works
Aller, M. I., Veale, E. L., Linden, A.-M., Sandu, C., Schwaninger, M., Evans, L. J., Korpi, E. R., Mathie, A. A., Wisden, W., & Brickley, S. G. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3153-05.2005 · Cited by 137 · see citing works
Self-citationEEG Responses to Visual Landmarks in Flying Pigeons
Vyssotski, A. L., Dell’Omo, G., Dell’Ariccia, G., Abramchuk, A. N., Serkov, A. N., Латанов, А. В., Loizzo, A., Wolfer, D. P., & Lipp, H. (2009) · Current Biology · doi:10.1016/j.cub.2009.05.070 · Cited by 134 · see citing works
Self-citationKirk, I. J. (1998) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(97)00015-8 · Cited by 130 · see citing works
Brickley, S. G., Aller, M. I., Sandu, C., Veale, E. L., Alder, F. G., Sambi, H., Mathie, A. A., & Wisden, W. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1427-07.2007 · Cited by 119 · see citing works
Self-citationLinden, A.-M., Sandu, C., Aller, M. I., Vekovischeva, O. Y., Rosenberg, P. H., Wisden, W., & Korpi, E. R. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.129544 · Cited by 116 · see citing works
Self-citationOddie, S., Stefanek, W., Kirk, I. J., & Bland, B. H. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-05-01948.1996 · Cited by 106 · see citing works
Leung, L.-W. S., & Vanderwolf, C. H. (1980) · Brain Research · doi:10.1016/0006-8993(80)90348-0 · Cited by 99 · see citing works
Mizumori, S. J. Y., Barnes, C. A., & McNaughton, B. L. (1989) · Brain Research · doi:10.1016/0006-8993(89)90303-x · Cited by 92 · see citing works
Aller, M. I., & Wisden, W. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.12.011 · Cited by 91 · see citing works
Self-citationState-Dependent Alterations in Hippocampal Oscillations in Serotonin 1A Receptor-Deficient Mice
Gordon, J. A., Lacefield, C., Kentros, C. G., & Hen, R. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1211-05.2005 · Cited by 81 · see citing works
Colom, L. V., Nassif, S., Dickson, C. T., Smythe, J. W., & Bland, B. H. (1991) · Hippocampus · doi:10.1002/hipo.450010406 · Cited by 75 · see citing works
Automated sleep staging in rat with a standard spreadsheet
Costa‐Miserachs, D., Portell-Cortés, I., Torras-García, M., & Morgado-Bernal, I. (2003) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(03)00229-2 · Cited by 54 · see citing works
Determinants of the Anesthetic Sensitivity of Two-pore Domain Acid-sensitive Potassium Channels
Andres-Enguix, I., Caley, A., Yustos, R., Schumacher, M. A., Spanu, P. D., Dickinson, R., Maze, M., & Franks, N. P. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610692200 · Cited by 52 · see citing works
Self-citationOddie, S., Kirk, I. J., Whishaw, I. Q., & Bland, B. H. (1997) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)02290-0 · Cited by 48 · see citing works
TASK-Like Conductances Are Present within Hippocampal CA1 Stratum Oriens Interneuron Subpopulations
Torborg, C. L., Berg, A. P., Jeffries, B. W., Bayliss, D. A., & McBain, C. J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1257-06.2006 · Cited by 46 · see citing works
Bland, B. H., & Colom, L. V. (1988) · Brain Research · doi:10.1016/0006-8993(88)91171-7 · Cited by 40 · see citing works
Lopes, C. M. B., Franks, N. P., & Lieb, W. R. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702069 · Cited by 37 · see citing works
Self-citationBland, B. H., Bland, C. E., Colom, L. V., Roth, S. H., Declerck, S., Dypvik, A. T., Bird, J., & Deliyannides, A. (2002) · Hippocampus · doi:10.1002/hipo.10044 · Cited by 18 · see citing works
Effects of Cholinergic Drugs on Neocortical EEG and Flash-Visual Evoked Potentials in the Mouse
Tebano, M. T., Luzi, M., Palazzesi, S., et al. (1999) · Neuropsychobiology · doi:10.1159/000026596 · Cited by 13 · see citing works
Sleep–wake effects of yohimbine and atropine in rats with a clomipramine-based model of depression
Mavanji, V., & Datta, S. (2002) · Neuroreport · doi:10.1097/00001756-200209160-00006 · Cited by 7 · see citing works
Drucker-Colı́n, R., Dreyfus, G., Durand-Chávez, L. M., et al. (1983) · Journal of Neuroscience Research · doi:10.1002/jnr.490090408 · Cited by 5 · see citing works
Carretero (1998) · doi:10.1175/1520-0477(1998)079
Flagged first, then by citations
Cited by
Sorted by citations
Control of sleep and wakefulness
Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012) · Physiological Reviews · doi:10.1152/physrev.00032.2011 · Cited by 1,477 · see citing works
The Biology of General Anesthesia from Paramecium to Primate
Kelz, M. B., & Mashour, G. A. (2019) · Current Biology · doi:10.1016/j.cub.2019.09.071 · Cited by 151 · see citing works
Brain areas that influence general anesthesia
Leung, L. S., Luo, T., Ma, J., & Herrick, I. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.08.001 · Cited by 126 · see citing works
Excitatory pathways from the lateral habenula enable propofol-induced sedation
Gelegen, C., Miracca, G., Ran, M. Z., Harding, E. C., Ye, Z., Yu, X., Tossell, K., Houston, C. M., Yustos, R., Hawkins, E. D., et al. (2018) · Current Biology · doi:10.1016/j.cub.2017.12.050 · Cited by 100 · see citing works
Self-citationMotoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics
Lazarenko, R. M., Willcox, S. C., Shu, S., Berg, A. P., Jevtovic-Todorovic, V., Talley, E. M., Chen, X., & Bayliss, D. A. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1655-10.2010 · Cited by 79 · see citing works
Cooper, A., Butto, T., Hammer, N., Jagannath, S., Fend-Guella, D. L., Akhtar, J., Radyushkin, K., Lesage, F., Winter, J., Strand, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13918-4 · Cited by 37 · see citing works
- Authors
- Pang, D. S. J., Robledo, C. J., Carr, D. R., Gent, T. C., Vyssotski, A. L., Caley, A., Zecharia, A. Y., Wisden, W., Brickley, S. G., & Franks, N. P.
- Affiliations
- Imperial College London (GB)
- University of Zurich (CH)
- UCL School of Pharmacy (GB)
- Corresponding author
- Pang, Daniel S. J.
- Robledo, Christian J.
- Franks, Nicholas P.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-10-13
- Volume
- 106
- Issue
- 41
- Pages
- 17546-17551
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2751655
- OpenAlex
- W2096377596
- Cited by
- 97
- References
- 51
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 3 · 2022: 11 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 6 · 2014: 9 · 2013: 6 · 2012: 8
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Biotechnology and Biological Sciences Research Council (G021691, BB/G021619/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- two-pore domain potassium channels, REM sleep, sleep onset, anesthetic sensitivity, halothane, cyclopropanes, cortical EEG, sleep fragmentation, knockout mice, sleep-wake transition
- MeSH terms
- Animals, Circadian Rhythm, Electroencephalography, Electromyography, Genotype, Oscillometry, Sleep, Wakefulness, Mice, Knockout, Potassium Channels, Tandem Pore Domain, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
