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| Subject Categories: Signal Transduction | Molecular Biology of Disease |
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| The EMBO Journal
(2006) 25, 2368–2376, doi:10.1038/sj.emboj.7601116 Published online 4 May 2006 |
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| TREK-1, a K+ channel involved in polymodal pain perception |
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| Abdelkrim Alloui1, Katharina Zimmermann2, Julien Mamet3, Fabrice Duprat3, Jacques Noël3, Jean Chemin3, 4, Nicolas Guy3, Nicolas Blondeau3, Nicolas Voilley3, Catherine Rubat-Coudert1, Marc Borsotto3, Georges Romey3, Catherine Heurteaux3, Peter Reeh2, Alain Eschalier1 and Michel Lazdunski3 |
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1 Laboratoire de Pharmacologie Médicale EA 3848 INSERM/Faculté de Médecine/CHU, Clermont-Ferrand, France 2 Department of Physiology and Pathophysiology, University Erlangen-Nuremberg, Erlangen, Germany 3 Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-Université de Nice, Institut Paul Hamel, Sophia Antipolis, Valbonne, France To whom correspondence should be addressed Michel Lazdunski, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-Université de Nice, Institut Paul Hamel, 660, Route des Lucioles, Sophia Antipolis, 06560 Valbonne, France. Tel.: +33 493 957702; Fax: +33 493 957704; E-mail: lazdunski@ipmc.cnrs.fr 4 Present address: Departement de Physiologie, Institut de Génomique Fonctionnelle, CNRS UMR 5203, INSERM U661, 141, rue de la Cardonille, 34094 Montpellier, France Received 11 January 2006; Accepted 4 April 2006; Published online 4 May 2006. |
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| Abstract |
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| The TREK-1 channel is a temperature-sensitive, osmosensitive and mechano-gated K+ channel with a regulation by Gs and Gq coupled receptors. This paper demonstrates that TREK-1 qualifies as one of the molecular sensors involved in pain perception. TREK-1 is highly expressed in small sensory neurons, is present in both peptidergic and nonpeptidergic neurons and is extensively colocalized with TRPV1, the capsaicin-activated nonselective ion channel. Mice with a disrupted TREK-1 gene are more sensitive to painful heat sensations near the threshold between anoxious warmth and painful heat. This phenotype is associated with the primary sensory neuron, as polymodal C-fibers were found to be more sensitive to heat in single fiber experiments. Knockout animals are more sensitive to low threshold mechanical stimuli and display an increased thermal and mechanical hyperalgesia in conditions of inflammation. They display a largely decreased pain response induced by osmotic changes particularly in prostaglandin E2-sensitized animals. TREK-1 appears as an important ion channel for polymodal pain perception and as an attractive target for the development of new analgesics. |
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| Keywords: pain, potassium channel, TREK-1 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHTREK-1 is a heat-activated background K + channel The EMBO Journal Article (01 Jun 2000) ASIC3, a sensor of acidic and primary inflammatory pain The EMBO Journal Article A phospholipid sensor controls mechanogating of the K + channel TREK-1 The EMBO Journal Article (12 Jan 2005) |
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