TREKing noxious thermosensation

Have you seen?6 May 2009free access TREKing noxious thermosensation Olaf Pongs Corresponding Author Olaf Pongs Institute für neurale Signalverarbeitung, Zentrum für Mol. Neurobiologie, University-Hospital Eppendorf, Hamburg, Germany Search for more papers by this author Olaf Pongs Corresponding Author Olaf Pongs Institute für neurale Signalverarbeitung, Zentrum für Mol. Neurobiologie, University-Hospital Eppendorf, Hamburg, Germany Search for more papers by this author Author Information Olaf Pongs 1 1Institute für neurale Signalverarbeitung, Zentrum für Mol. Neurobiologie, University-Hospital Eppendorf, Hamburg, Germany *Corresponding author. Institute für neurale Signalverarbeitung, Zentrum für Mol. Neurobiologie, Martinistr. 52/Falkenried 94, 1st Floor, Room 163, Hamburg D-20251, Germany. E-mail: [email protected] The EMBO Journal (2009)28:1195-1196https://doi.org/10.1038/emboj.2009.107 There is an Article (May 2009) associated with this Have you seen ...?. PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The ability to sense environmental temperature as pleasant or unpleasant is associated with the activity of thermo-sensitive neurons in the peripheral nervous system. Differential sensation of pleasant environmental temperatures (warm and cool) versus unpleasant and noxious (cold and hot) temperatures requires the definition of thresholds and temperature ranges for activating thermonociceptors. In this issue of The EMBO Journal, a study by Noël et al (2009) entitled 'The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception' shows that the potassium leak channels TREK-1 and TRAAK have an important regulatory role in noxious thermonociceptors to ensure a high-enough activation threshold that does not interfere with the sensing of innocuous (warm and cool) temperature, but low enough in order to avoid tissue damage. Of the five senses—sight, hearing, smell, taste, and touch—touch is perhaps the most varied. Touch describes the ability to sense chemical stimuli, mechanical forces, and temperature. Temperature sensing comes essentially in two flavours: pleasant (innocuous) and unpleasant (noxious). In the peripheral nervous systems, at the level of the skin two basic classes of innocuous- and noxious-temperature-sensing neurons have been recognized: myelinated Aδ-fibres responsible for the first sharp pain, and C-fibres responsible for the slow, longer-lasting nociception of noxious temperature (Kandel et al, 2000). A major breakthrough in the identification of molecules involved in temperature sensing was the discovery of temperature-activated transient receptor potential (TRP) ion channels that were directly gated by a change in temperature. Four heat-activated TRP ion channels (TRPV1–4) and two cold-sensitive TRP ion channels (TRPM8 and TRPA1) were identified. Recently, two studies (Brauchi et al, 2004; Voets et al, 2004) convincingly have argued that the temperature-sensing properties of TRPM8 and TRPV1 channels arise directly from intrinsic thermodynamic channel properties. Whether this also applies to the other TRP channels is still a matter of debate (Dhaka et al, 2006). Importantly, TRPM8 and TRPV1 are voltage activated and temperature shifts the voltage-dependent activation of the channels to more physiological ranges. The implication of this observation is that membrane potential plays an important role in the temperature-sensing activity of the TRP channels. Given the sophistication of thermo-sensitivity, it most likely involves complex interactions of ion channels, receptors, and proteins in addition to TRP channel activation. A report in this issue of The EMBO Journal by Noël et al (2009) has well characterized one important player in this complex game. Investigating thermosensitivity in TREK-1/TRAAK double knock-out mice, it was observed that both K+ channels control the response of sensory neurons to hot and cold. TREK-1 and TRAAK are dimeric, two-pore domain potassium (K2P) channels belonging to the TWIK-channel family (TWIK—tandem of P domains in a weak inwardly-rectifying K+ channel) (Talley et al, 2003). K2P channels are leak channels that are open at all membrane voltages and, therefore, are involved in controlling the resting membrane potential. Importantly, the two K2P channels are activated by certain anaesthetics, membrane stretching, intracellular acidosis, and by heat (Maingret et al, 1999a, 1999b, 2000; Patel et al, 1999). Loss of TREK-1 and TRAAK channel activity in the TREK-1, TRAAK double knockout mouse apparently has two important consequences. Firstly, the firing threshold of thermosensitive neurons is lowered, resulting in an increased firing activity in response to a change in temperature. Secondly, the population of sensory neurons is increased, which respond to relatively mild changes in temperature. These two effects highlight the important interplay of depolarizing TRP and repolarizing K2P channel activity to control the threshold for sensory neuron activation. In detail, the measured cell-physiological and phenotypical effects could be divided into several informative subgroups (see Figure 1). The results shed light on the mystery behind how sensory neurons set the alarm off when noxious cold or hot temperatures are encountered. Also, the data concur with the notion that nociceptive thresholds are not fixed and can be lowered or elevated to modulate the responsiveness of the sensory neurons. Changes in threshold are associated with clinical pain syndromes (Scholz and Woolf, 2002). It will be interesting to see how this type of neural plasticity relates to altered K2P channel activity. Possibly, the new data on the role of K2P channels in nociception open new avenues for more effective therapies in pain treatment. Figure 1.Temperature sensing at peripheral terminals of unmyelinated C-fibres (thin axons) and myelinated Aδ-fibres (thick axons) is transmitted to the spinal cord, and from there onwards to the cortex via central pathways. The diagram illustrates schematically ion channel populations in four subgroups of sensory neurons investigated in the study of Noël et al (2009). One group represented capsaicin-insensitive, heat-sensitive C-fibres, probably expressing TRPV3 and TRPPV4 channels, which responded to temperature increases between 30 and ∼48°C (coloured in yellow). The population of these neurons was markedly increased in the TREK−/−, TRAAK−/− double knockout mice. A second group corresponded to heat-sensitive, capsaicin-sensitive, TRPV1-expressing Aδ neurons (coloured in red), which are normally in charge of signalling high temperature (⩾50°C)-induced pain, but were activated within a significantly lower temperature range. On the cold side, a small population of neurons (lightly blue coloured, Aδ fibres?) sensitive to menthol, allyl-isothiocyanate (AI) and cold is increased. However, the major effect concerns the population of menthol- and AI-insensitive and cold-sensitive C-fibre neurons (coloured in blue) that are normally active only at temperatures below 12°C. The question mark indicates that the nature of the cold-sensing excitatory ion channel is unclear. In the double knockout mice the population of these sensory neurons is significantly increased and their response activity is shifted to temperatures between 30 and 12°C. Download figure Download PowerPoint References Brauchi S, Orio P, Latorre R (2004) Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc Natl Acad Sci USA 101: 15494–15499CrossrefCASPubMedWeb of Science®Google Scholar Dhaka A, Viswanath V, Patapoutian A (2006) Trp ion channels and temperature sensation. Annu Rev Neurosci 29: 135–161CrossrefCASPubMedWeb of Science®Google Scholar Kandel ER, Schwartz JH, Jessel TM (2000) Principles of Neural Science. New-York: McGraw HillPubMedGoogle Scholar Maingret F, Fosset M, Lesage F, Lazdunski M, Honore E (1999a) TRAAK is a mammalian neuronal mechano-gated K+ channel. J Biol Chem 274: 1381–1387CrossrefCASPubMedWeb of Science®Google Scholar Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, Lazdunski M, Honore E (2000) TREK-1 is a heat-activated background K(+) channel. EMBO J 19: 2483–2491Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore E (1999b) Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 274: 26691–26696CrossrefCASPubMedWeb of Science®Google Scholar Noël J, Zimmermann K, Busserolles J, Deval E, Alloui A, Diochot S, Guy N, Borsotto M, Reeh P, Eschalier A, Lazdunski M (2009) The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception. EMBO J 28: 1308–1318Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 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: 422–426CrossrefCASPubMedWeb of Science®Google Scholar Scholz J, Woolf CJ (2002) Can we conquer pain? Nat Neurosci 5 (Suppl): 1062–1067CrossrefCASPubMedWeb of Science®Google Scholar Talley EM, Sirois JE, Lei Q, Bayliss DA (2003) Two-pore-domain (KCNK) potassium channels: dynamic roles in neuronal function. Neuroscientist 9: 46–56CrossrefCASPubMedWeb of Science®Google Scholar Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430: 748–754CrossrefCASPubMedWeb of Science®Google Scholar Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 28,Issue 9,May 6, 2009Four genomes The illustration shows syntenic relationships between human, chimpanzee, mouse and zebrafish genomes. Curved links encode sequence similarity and outer data tracks represent consensus similarity statistics and orthologous genes. The cover image shows a detail of a visualization prepared with the free genome comparison tool, Circos. Martin Krzywinski, a research scientist at Canada's Michael Smith Genome Sciences Center, is interested in fingerprinting, data analysis and data visualization. Visit the website at http://mkweb.bcgsc.ca/circos for more information on Circos and other activities and projects of Martin Krzywinski. Volume 28Issue 96 May 2009In this issue FiguresReferencesRelatedDetailsLoading ...

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