Background K+ channels are dimers of K2P channel subunits, each of which is composed of four transmembrane segments and two P domains arranged in tandem.
The Aplysia serotonin-sensitive S-type K+ channel and the Lymnaea anaesthetic-sensitive K(An) channels are classical examples of background K+ channels.
Background K+ channels and their regulation by membrane-receptor-coupled second messengers, as well as pharmacological agents, influence neuronal resting membrane potential, action potential duration, membrane input resistance and, consequently, neurotransmitter release.
K2P channels diverge from the constant-field Goldman–Hodgkin–Katz (GHK) current formulation and are characterized by complex permeation and gating mechanisms.
TREK1 can be activated by mechanical stimulation, intracellular acidosis and warm temperature, thus qualifying as a polymodal sensory ion channel integrating multiple physical and chemical stimuli.
Besides its activation by physical stimuli, TREK1 is also upmodulated by various chemical stimuli including cellular lipids and volatile general anaesthetics.
Recent evidence suggests that both mechanical and lipid activations of TREK1 may be functionally linked. The proposed model states that a tight dynamic interaction of the cytosolic carboxy-terminal domain of TREK1 with the inner leaflet of the plasma membrane is central to the mechanism of channel gating and regulation by membrane receptors/second messenger pathways.
TREK1 is downmodulated by the stimulation of both Gs- and Gq-coupled membrane receptors. Recent studies have identified the second messenger pathways involved in this regulation, including phosphorylation pathways and PtdIns(4,5)P2 hydrolysis.
The Trek1−/− mutant mice are healthy, fertile and do not display any visible morphological difference. However, recent studies indicate a central role for TREK1 in anaesthesia, neuroprotection, pain perception and depression.
Both the Aplysia S-type K+ channel and mammalian TREK1 are involved in controlling the excitability of presynaptic neurons through the pathway mediated by serotonin, cyclic AMP and protein kinase A. However, in the dorsal raphé neurons, serotonin probably opens TREK1 though the Gi/o pathway, whereas serotonin closes the S-type K+ channel through the Gs pathway in molluscan sensory neurons.
Two-pore-domain K+ (K2P) channel subunits are made up of four transmembrane segments and two pore-forming domains that are arranged in tandem and function as either homo- or heterodimeric channels. This structural motif is associated with unusual gating properties, including background channel activity and sensitivity to membrane stretch. Moreover, K2P channels are modulated by a variety of cellular lipids and pharmacological agents, including polyunsaturated fatty acids and volatile general anaesthetics. Recent in vivo studies have demonstrated that TREK1, the most thoroughly studied K2P channel, has a key role in the cellular mechanisms of neuroprotection, anaesthesia, pain and depression.
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Castellucci, V. & Kandel, E. R. Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia. Science 194, 1176–1178 (1976). Study of the neural circuit of the gill-withdrawal reflex in the isolated abdominal ganglion of Aplysia , indicating that short-term sensitization is due to presynaptic facilitation.
Siegelbaum, S. A., Camardo, J. S. & Kandel, E. R. Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature 299, 413–417 (1982). Shows that the application of serotonin to the cell body or intracellular injection of cAMP causes prolonged and complete closure of the S-type background K+ channel, which can account for the increases in transmitter release which underlie behavioural sensitization.
Franks, N. P. & Lieb, W. R. Volatile general anaesthetics activate a novel neuronal K+ current. Nature 333, 662–664 (1988). Shows that, amongst a group of apparently identical molluscan neurons having endogenous firing activity, a single cell displays an unusual sensitivity to volatile agents due to a novel anaesthetic-activated background K+ current IK(An).
Franks, N. P. & Lieb, W. R. Stereospecific effects of inhalational general anesthetic optical isomers on nerve ion channels. Science 254, 427–430 (1991).
Byrne, J. H. & Kandel, E. R. Presynaptic facilitation revisited: state and time dependence. J. Neurosci. 16, 425–435 (1996).
Patel, A. J. et al. A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J. 17, 4283–4290 (1998). Demonstrates that TREK1 shares the functional properties of the Aplysia S channel.
Honoré, E., Patel, A. J., Chemin, J., Suchyna, T. & Sachs, F. Desensitization of mechano-gated K2P channels. Proc. Natl Acad. Sci. USA 103, 6859–6864 (2006).
Heurteaux, C. et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nature Neurosci. 9, 1134–1141 (2006). Shows that TREK1-deficient ( Kcnk2−/−) mice have an increased efficacy of 5-HT neurotransmission and a resistance to depression.
Alloui, A. et al. TREK-1, a K+ channel involved in polymodal pain perception. EMBO J. 25, 2368–2376 (2006).
Heurteaux, C. et al. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J. 23, 2684–2695 (2004).
Patel, A. J. et al. Inhalational anaesthetics activate two-pore-domain background K+ channels. Nature Neurosci. 2, 422–426 (1999). Shows that the K 2P channels TASK and TREK1 are activated by volatile general anaesthetics. Chloroform, diethyl ether, halothane and isoflurane activate TREK1, whereas only halothane and isoflurane activate TASK.
Gruss, M. et al. Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol. Pharmacol. 65, 443–452 (2004).
Hervieu, G. J. et al. Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS. Neuroscience 103, 899–919 (2001).
Medhurst, A. D. et al. Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Mol. Brain Res. 86, 101–114 (2001).
Fink, M. et al. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 15, 6854–6862 (1996).
Talley, E. M., Solorzano, G., Lei, Q., Kim, D. & Bayliss, D. A. CNS distribution of members of the two-pore-domain (KCNK) potassium channel family. J. Neurosci. 21, 7491–7505 (2001).
Patel, A. J. & Honoré, E. Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci. 24, 339–346 (2001).
Lesage, F. & Lazdunski, M. Molecular and functional properties of two-pore-domain potassium channels. Am. J. Physiol. Renal. Physiol. 279, F793–F801 (2000).
Goldstein, S. A. N., Bockenhauer, D., O'Kelly, I. & Zilberg, N. Potassium leak channels and the KCNK family of two-P-domain subunits. Nature Rev. Neurosci. 2, 175–184 (2001).
Talley, E. M., Sirois, J. E., Lei, Q. & Bayliss, D. A. Two-pore-domain (KCNK) potassium channels: dynamic roles in neuronal function. Neuroscientist 9, 46–56 (2003).
Kim, D. Fatty acid-sensitive two-pore domain K+ channels. Trends Pharmacol. Sci. 24, 648–654 (2003).
Doyle, D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69–77 (1998). Uses x-ray analysis to reveal that four identical KcsA subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids.
O''Connell, A. D., Morton, M. J. & Hunter, M. Two-pore domain K+ channels-molecular sensors. Biochim. Biophys. Acta 1566, 152–161 (2002).
Patel, A. J., Lazdunski, M. & Honoré, E. Lipid and mechano-gated 2P domain K+ channels. Curr. Opin. Cell Biol. 13, 422–428 (2001).
Czirjak, G. & Enyedi, P. Formation of functional heterodimers between the TASK-1 and TASK-3 two pore domain potassium channel subunits. J. Biol. Chem. 277, 5436–5432 (2001).
Kang, D., Han, J., Talley, E. M., Bayliss, D. A. & Kim, D. Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells. J. Physiol. 554, 64–77 (2004).
Xian Tao, L. et al. The stretch-activated potassium channel TREK-1 in rat cardiac ventricular muscle. Cardiovasc. Res. 69, 86–97 (2006).
Bockenhauer, D., Zilberberg, N. & Goldstein, S. A. KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nature Neurosci. 4, 486–491 (2001).
Lesage, F. et al. A pH-sensitive yeast outward rectifier K+ channel with two pore domains and novel gating properties. J. Biol. Chem. 271, 4183–4187 (1996).
Reid, J. D. et al. The S. cerevisiae outwardly-rectifying potassium channel (DUK1) identifies a new family of channels with duplicated pore domains. Recept. Channels 4, 51–62 (1996).
Zhou, X. L., Vaillant, B., Loukin, S. H., Kung, C. & Saimi, Y. YKC1 encodes the depolarization-activated K+ channel in the plasma membrane of yeast. FEBS Lett. 373, 170–176 (1995).
Ketchum, K. A., Joiner, W. J., Sellers, A. J., Kaczmarek, L. K. & Goldstein, S. A. N. A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem. Nature 376, 690–695 (1995).
Lesage, F. et al. TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J. 15, 1004–1011 (1996). Cloning of the first mammalian K 2P channel subunit TWIK1.
Duprat, F. et al. TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J. 16, 5464–5471 (1997).
Goldstein, S. A., Price, L. A., Rosenthal, D. N. & Pausch, M. H. ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 93, 13256–13261 (1996).
Fink, M. et al. A neuronal two P domain K+ channel activated by arachidonic acid and polyunsaturated fatty acid. EMBO J. 17, 3297–3308 (1998).
Reyes, R. et al. Cloning and expression of a novel pH-sensitive two pore domain potassium channel from human kidney. J. Biol. Chem. 273, 30863–30869 (1998).
Lesage, F., Terrenoire, C., Romey, G. & Lazdunski, M. 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 (2000).
Hille, B. Ion Channels of Excitable Membranes (Sinauer, Sunderland, Massachusetts, 1992).
Ilan, N. & Goldstein, S. A. Kcnko: single, cloned potassium leak channels are multi-ion pores. Biophys. J. 80, 241–253 (2001).
Maingret, F., Honoré, E., Lazdunski, M. & Patel, A. J. Molecular basis of the voltage-dependent gating of TREK-1, a mechano- sensitive K+ channel. Biochem. Biophys. Res. Commun. 292, 339–346 (2002).
Lopes, C. M., Gallagher, P. G., Buck, M. E., Butler, M. H. & Goldstein, S. A. Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3. J. Biol. Chem. 275, 16969–16978 (2000).
Chemin, J. et al. A phospholipid sensor controls mechanogating of the K+ channel TREK-1. EMBO J. 24, 44–53 (2005). Shows that membrane phospholipids, including PtdIns(4,5)P 2 , control channel gating and transform TREK1 into a leak K+ conductance. A C-terminal positively charged cluster is the phospholipid-sensing domain that interacts with the plasma membrane.
Patel, A. J. & Honoré, E. Anesthetic-sensitive 2P domain K+ channels. Anesthesiology 95, 1013–1025 (2001).
Maylie, J. & Adelman, J. P. Beam me up, Scottie! TREK channels swing both ways. Nature Neurosci. 4, 457–458 (2001).
Lopes, C. M. et al. PiP2-Hydrolysis underlies agonist-induced inhibition and regulates voltage-gating of 2-P-Domain K+ Channels. J. Physiol. 564, 117–129 (2005).
Maingret, F. et al. TREK-1 is a heat-activated background K+ channel. EMBO J. 19, 2483–2491 (2000).
Honoré, E., Maingret, F., Lazdunski, M. & Patel, A. J. An intracellular proton sensor commands lipid- and mechano-gating of the K+ channel TREK-1. EMBO J. 21, 2968–2976 (2002).
Kang, D., Choe, C. & Kim, D. Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. J. Physiol. 564, 103–116 (2005).
Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M. & Honoré, E. Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J. Biol. Chem. 274, 26691–26696 (1999).
Lauritzen, I. et al. Cross-talk between the mechano-gated K2P channel TREK-1 and the actin cytoskeleton. EMBO Rep. 6, 642–648 (2005).
Sandoz, G. et al. AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K+ channels into open leak channels. EMBO J. 25, 5864–5872 (2006).
Murbartian, J., Lei, Q., Sando, J. J. & Bayliss, D. A. Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. J. Biol. Chem. 280, 30175–30184 (2005).
Sheetz, M. P. & Singer, S. J. Biological membranes as bilayer couples. A molecular mechanism of drug-erythocyte interactions. Proc. Natl Acad. Sci. USA 71, 4457–4461 (1974). Shows that membranes whose polar lipids are distributed asymmetrically in the two halves of the membrane bilayer can act as bilayer couples, that is, the two halves can respond differently to a perturbation. This hypothesis is applied to the interactions of amphipathic drugs with human erythrocytes.
Martinac, B., Adler, J. & Kung, C. Mechanosensitive ion channels of E. coli activated by amphipaths. Nature 348, 261–263 (1990).
Kim, Y., Gnatenco, C., Bang, H. & Kim, D. Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi . Pflugers Arch. 2001, 952–960 (2001).
Kim, Y., Bang, H., Gnatenco, C. & Kim, D. 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 (2001).
Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M. & Honoré, E. Lysophospholipids open the two P domain mechano-gated K+ channels TREK-1 and TRAAK. J. Biol. Chem. 275, 10128–10133 (2000).
Chemin, J. et al. Lysophosphatidic acid-operated K+ channels. J. Biol. Chem. 280, 4415–4421 (2005).
Chemin, J. et al. Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels. EMBO J. 22, 5403–5411 (2003).
Koh, S. D. et al. TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. J. Biol. Chem. 47, 44338–44346 (2001).
Kennard, L. E. et al. Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine. Br. J. Pharmacol. 144, 821–829 (2005).
Franks, N. P. & Honoré, E. The TREK K2P channels and their role in general anaesthesia and neuroprotection. Trends Pharmacol. Sci. 25, 601–608 (2004).
Franks, N. P. & Lieb, W. R. Background K+ channels: an important target for volatile anesthetics? Nature Neurosci. 2, 395–396 (1999).
Harinath, S. & Sikdar, S. K. Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels. Neuropharmacology 46, 750–760 (2004).
Buckler, K. J. & Honoré, E. The lipid-activated two-pore domain K+ channel TREK-1 is resistant to hypoxia: implication for ischaemic neuroprotection. J. Physiol. 562, 213–222 (2005).
Caley, A. J., Gruss, M. & Franks, N. P. The effects of hypoxia on the modulation of human TREK-1 potassium channels. J. Physiol. 562, 205–212 (2004).
Blondeau, N., Widmann, C., Lazdunski, M. & Heurteaux, C. Polyunsaturated fatty acids induce ischemic and epileptic tolerance. Neuroscience 109, 231–241 (2002).
Blondeau, N., Lauritzen, I., Widmann, C., Lazdunski, M. & Heurteaux, C. A potent protective role of lysophospholipids against global cerebral ischemia and glutamate excitotoxicity in neuronal cultures. J. Cereb. Blood Flow Metab. 22, 821–834 (2002).
Lang-Lazdunski, L., Blondeau, N., Jarretou, G., Lazdunski, M. & Heurteaux, C. Linolenic acid prevents neuronal cell death and paraplegia after transient spinal cord ischemia in rats. J. Vasc. Surg. 38, 564–575 (2003).
Lauritzen, I. et al. Poly-unsaturated fatty acids are potent neuroprotectors. EMBO J. 19, 1784–1793 (2000).
Duprat, F. et al. The neuroprotective agent riluzole activates the two P domain K+ channels TREK-1 and TRAAK. Mol. Pharmacol. 57, 906–912 (2000).
Clapham, D. E. TRP channels as cellular sensors. Nature 426, 517–524 (2003).
Nilius, B., Owsianik, G., Voets, T. & Peters, J. A. Transient receptor potential cation channels in disease. Physiol. Rev. 87, 165–217 (2007).
Gordon, J. A. & Hen, R. TREKing toward new antidepressants. Nature Neurosci. 9, 1081–1083 (2006).
Maingret, F., Fosset, M., Lesage, F., Lazdunski, M. & Honoré, E. TRAAK is a mammalian neuronal mechano-gated K+ channel. J. Biol. Chem. 274, 1381–1387 (1999).
Byrne, J. H. & Kandel, E. R. Presynaptic facilitation revisited: state and time dependence. J. Neurosci. 16, 425–435 (1996).
Shuster, M. J., Camardo, J. S., Siegelbaum, S. A. & Kandel, E. R. Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches. Nature 313, 392–395 (1985).
Sweatt, D. J. et al. FMRFamide reverses protein phosphorylation produced by 5-HT and cAMP in Aplysia sensory neurons. Nature 342, 275–278 (1989).
Belardetti, F., Kandel, E. R. & Siegelbaum, S. A. Neuronal inhibition by the peptide FMRFamide involves opening of S K+ channels. Nature 325, 153–156 (1987). Demonstrates that FMRFamide produces two actions on the S channel; it increases the probability of opening of the S channels via a cAMP-independent second-messenger system, and it reverses the closures of S channels produced by serotonin or cAMP.
Hamill, O. P. & Martinac, B. Molecular basis of mechanotransduction in living cells. Physiol. Rev. 81, 685–740 (2001).
Sachs, F. & Morris, C. E. Mechanosensitive ion channels in nonspecialized cells. Rev. Physiol. Biochem. Pharmacol. 132, 1–77 (1998).
Kung, C. A possible unifying principle for mechanosensation. Nature 436, 647–654 (2005).
Kloda, A., Ghazi, A. & Martinac, B. C-terminal charged cluster of MscL, RKKEE, functions as a pH sensor. Biophys. J. 90, 1992–1998 (2006).
Wei, A., Jegla, T. & Salkoff, L. Eight potassium channel families revealed by the C. elegans genome project. Neuropharmacology 35, 805–829 (1996).
Czempinski, K., Zimmermann, S., Ehrhardt, T. & Muller-Rober, B. New structure and function in plant K+ channels: KCO1, an outward rectifier with a steep Ca2+ dependency. EMBO J. 16, 2565–2575 (1997).
Bayliss, D. A., Talley, E. M., Sirois, J. E. & Lei, Q. TASK-1 is a highly modulated pH-sensitive ''leak'' K+ channel expressed in brainstem respiratory neurons. Respir. Physiol. 129, 159–174 (2001).
Talley, E. M., Lei, Q., Sirois, J. E. & Bayliss, D. A. TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. Neuron 25, 399–410 (2000).
Talley, E. M. & Bayliss, D. A. Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action. J. Biol. Chem. 277, 17733–17742 (2002).
Kim, D., Fujita, A., Horio, Y. & Kurachi, Y. Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Circ. Res. 82, 513–518 (1998).
Lesage, F. Pharmacology of neuronal background potassium channels. Neuropharmacology 44, 1–7 (2003).
Plant, L. D., Rajan, S. & Goldstein, S. A. K2P channels and their protein partners. Curr. Opin. Neurobiol. 15, 326–333 (2005).
Rajan, S., Plant, L. D., Rabin, M. L., Butler, M. H. & Goldstein, S. A. Sumoylation silences the plasma membrane leak K+ channel K2P1 . Cell 121, 37–47 (2005).
Decressac, S. et al. ARF6-dependent interaction of the TWIK1 K+ channel with EFA6, a GDP/GTP exchange factor for ARF6. EMBO Rep. 5, 1171–1175 (2004).
Girard, C. et al. p11, an annexin II subunit, an auxilary protein associated with the background K+ channel, TASK-1. EMBO J. 21, 4439–4448 (2002).
Renigunta, V. et al. The retention factor p11 confers an endoplasmic reticulum-localization signal to the potassium channel TASK-1. Traffic 7, 168–181 (2006).
O'Kelly, I., Butler, M. H., Zilberberg, N. & Goldstein, S. A. Forward transport: 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell 111, 577–588 (2002).
Hsu, K., Seharaseyon, J., Dong, P., Bour, S. & Marban, E. Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol. Cell 14, 259–267 (2004).
I am grateful to the ANR 2005 Cardiovasculaire-obésité-diabète, to the Association for Information and Research on Genetic Kidney Disease France, to the Fondation del Duca, to the Fondation de France, to the Fondation de la Recherche Médicale, to EEC Marie-Curie fellowships, to INSERM and to CNRS for support. I wish to thank A. Patel, S. Siegelbaum and E. Kandel for critical reading of this manuscript. I am grateful to M. Lazdunski and colleagues for helpful and stimulating discussions. Finally, I would like to thank the reviewers of this manuscript for their constructive input.
The author declares no competing financial interests.
- P domain
A short amino acid segment between two transmembrane helices that dips into the membrane without fully crossing it.
- Selectivity filter
The sequence that determines K+ selectivity of K+ channels. The primary sequence of the P loop of most K+ channels has the signature sequence Thr–Val–Gly–Tyr–Gly.
- Permeability ratio
The relative permeability of an ion channel for a particular monovalent cation. A given ion channel can allow the passage of related ionic species, although not all with the same ease.
The property whereby current through a channel does not flow with the same ease from the inside as from the outside.
- Inward rectifiers
Channels that allow long depolarizing responses, as they close during depolarizing pulses and open with steep voltage dependence upon hyperpolarization. They are called inward rectifiers because current flows through them more easily into than out of the cell.
- Outward rectifiers
Channels that allow current to flow more easily out of the cell. Voltage-gated K+ channels are outward rectifiers that shape the action potential duration.
- Intracellular acidosis
A decrease in intracellular pH that occurs, for example, during brain ischaemia.
- Cell-attached patch configuration
Recording configuration in which the patch of membrane at the tip of the recording electrode is not excised but remains attached to the cell. This configuration allows the measurement of the current flowing through the ion channels embedded in the electrically isolated membrane patch.
- Inside-out patch configuration
Recording configuration in which the patch of membrane at the tip of the patch-clamp electrode is excised from the cell. The intracellular side of the channel is exposed to the bathing solution.
Decrease in the activity of a protein during maintained stimulation.
- Inner leaflet
The inner layer of phospholipids in the plasma membrane.
- Polar head
Hydrophilic charged groups such as choline, ethanolamine, serine or inositol, bound to glycerol phosphate in membrane phospholipids.
A molecule with both hydrophobic and hydrophilic surfaces.
- Outside-out patch configuration
A variant of the patch-clamp technique, in which a patch of plasma membrane is excised from the cell. The outside of the membrane is exposed to the bathing solution.
- Polymodal C-fibres
Non-myelinated axons characterized by a slow conduction. Polymodal nociceptors are activated by high intensity mechanical, chemical and thermal stimuli, involving non-myelinated C-fibres conducting delayed pain.
The perception of a stimulus as painful when previously the same stimulus was reported to be non-painful.
- Porsolt forced swim test
A method to estimate behavioural despair in a stressful and inescapable situation. Mice rapidly adopt a characteristic immobile posture when they are forced to swim in a water tank. Immobility is considered to be a state of 'lowered mood' in which the animal has given up hope of finding an exit and is resigned to the stressful situation.
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Honoré, E. The neuronal background K2P channels: focus on TREK1. Nat Rev Neurosci 8, 251–261 (2007). https://doi.org/10.1038/nrn2117
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