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TREK‐1, a K + channel involved in polymodal pain perception
Author(s) -
Alloui Abdelkrim,
Zimmermann Katharina,
Mamet Julien,
Duprat Fabrice,
Noël Jacques,
Chemin Jean,
Guy Nicolas,
Blondeau Nicolas,
Voilley Nicolas,
RubatCoudert Catherine,
Borsotto Marc,
Romey Georges,
Heurteaux Catherine,
Reeh Peter,
Eschalier Alain,
Lazdunski Michel
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601116
Subject(s) - trpv1 , nociceptor , mechanosensation , ion channel , sensory system , transient receptor potential channel , biology , hyperalgesia , capsaicin , neuroscience , nociception , sensory neuron , perception , pain perception , microbiology and biotechnology , receptor , biochemistry , medicine , anesthesia
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 E 2 ‐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.