title: Ion channel profile of TRPM8 cold receptors reveals a role of TASK-3 potassium channels in thermosensation.
abstract: Animals sense cold ambient temperatures through the activation of peripheral thermoreceptors that express TRPM8, a cold- and menthol-activated ion channel. These receptors can discriminate a very wide range of temperatures from innocuous to noxious. The molecular mechanism responsible for the variable sensitivity of individual cold receptors to temperature is unclear. To address this question, we performed a detailed ion channel expression analysis of cold-sensitive neurons, combining bacterial artificial chromosome (BAC) transgenesis with a molecular-profiling approach in fluorescence-activated cell sorting (FACS)-purified TRPM8 neurons. We found that TASK-3 leak potassium channels are highly enriched in a subpopulation of these sensory neurons. The thermal threshold of TRPM8 cold neurons is decreased during TASK-3 blockade and in mice lacking TASK-3, and, most importantly, these mice display hypersensitivity to cold. Our results demonstrate a role of TASK-3 channels in thermosensation, showing that a channel-based combinatorial strategy in TRPM8 cold thermoreceptors leads to molecular specialization and functional diversity.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain. Electronic address: cruz@umh.es.
authors.forename: Cruz
authors.initials: C
authors.lastname: Morenilla-Palao
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain.
authors.forename: Enoch
authors.initials: E
authors.lastname: Luis
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Peña
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Quintero
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Janelle L
authors.initials: JL
authors.lastname: Weaver
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bayliss
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain. Electronic address: felix.viana@umh.es.
authors.forename: Félix
authors.initials: F
authors.lastname: Viana
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003080:Cold Temperature; D051379:Mice; D020671:Posterior Horn Cells / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D012684:Sensory Thresholds; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D013697:Thermosensing
chemical_list: D015221:Potassium Channels; C511784:TASK3 protein, mouse; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse