Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation
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 variab...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714006664 |
| _version_ | 1818331171956719616 |
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| author | Cruz Morenilla-Palao Enoch Luis Carlos Fernández-Peña Eva Quintero Janelle L. Weaver Douglas A. Bayliss Félix Viana |
| author_facet | Cruz Morenilla-Palao Enoch Luis Carlos Fernández-Peña Eva Quintero Janelle L. Weaver Douglas A. Bayliss Félix Viana |
| author_sort | Cruz Morenilla-Palao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T13:15:37Z |
| format | Article |
| id | doaj.art-ca7d43b6c075413ea13af2ff9360b359 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T13:15:37Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ca7d43b6c075413ea13af2ff9360b3592022-12-21T23:44:33ZengElsevierCell Reports2211-12472014-09-01851571158210.1016/j.celrep.2014.08.003Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in ThermosensationCruz Morenilla-Palao0Enoch Luis1Carlos Fernández-Peña2Eva Quintero3Janelle L. Weaver4Douglas A. Bayliss5Félix Viana6Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, SpainDepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USADepartment of Pharmacology, University of Virginia, Charlottesville, VA 22908, USAInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, SpainAnimals 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.http://www.sciencedirect.com/science/article/pii/S2211124714006664 |
| spellingShingle | Cruz Morenilla-Palao Enoch Luis Carlos Fernández-Peña Eva Quintero Janelle L. Weaver Douglas A. Bayliss Félix Viana Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation Cell Reports |
| title | Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation |
| title_full | Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation |
| title_fullStr | Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation |
| title_full_unstemmed | Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation |
| title_short | Ion Channel Profile of TRPM8 Cold Receptors Reveals a Role of TASK-3 Potassium Channels in Thermosensation |
| title_sort | ion channel profile of trpm8 cold receptors reveals a role of task 3 potassium channels in thermosensation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714006664 |
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