Slick potassium channels limit TRPM3-mediated activation of sensory neurons
Heat sensation is mediated by specialized heat-sensitive neurons in the somatosensory system that innervates the skin. Previous studies revealed that noxious heat sensation is controlled by the sodium (Na+)-activated potassium (K+) channel Slick (Kcnt2), which is highly expressed in nociceptive Aδ-f...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1459735/full |
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| author | Patrick Engel Fangyuan Zhou Bang Tam Thi Tran Achim Schmidtko Ruirui Lu |
| author_facet | Patrick Engel Fangyuan Zhou Bang Tam Thi Tran Achim Schmidtko Ruirui Lu |
| author_sort | Patrick Engel |
| collection | DOAJ |
| description | Heat sensation is mediated by specialized heat-sensitive neurons in the somatosensory system that innervates the skin. Previous studies revealed that noxious heat sensation is controlled by the sodium (Na+)-activated potassium (K+) channel Slick (Kcnt2), which is highly expressed in nociceptive Aδ-fibers. However, the mechanism by which Slick modulates heat sensation is poorly understood. Here, we generated mice lacking Slick conditionally in sensory neurons expressing Nav1.8 (SNS-Slick−/− mice). In SNS-Slick−/− mice, the latency to express any nocifensive behavior was reduced in the hot plate and tail immersion tests. In situ hybridization experiments revealed Slick was highly co-expressed with the essential heat sensor, transient receptor potential (TRP) melastatin (TRPM) 3, but not with TRP vanilloid 1, TRP ankyrin 1, or TRPM2 in sensory neurons. Notably, SNS-Slick−/− mice exhibited increased nocifensive behaviors following intraplantar injection of the TRPM3 activator pregnenolone sulfate. Patch-clamp recordings detected increased Na+-dependent outward K+ current (IK) after TRPM3 activation in sensory neurons, which showed no prominent IK after the replacement of NaCl with choline chloride. Thus, our study suggests that Slick limits TRPM3-mediated activation of sensory neurons, thereby inhibiting noxious heat sensing. |
| format | Article |
| id | doaj-art-0df9bc99a20d4dc18e6d3158fe9aae3d |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-0df9bc99a20d4dc18e6d3158fe9aae3d2025-08-20T02:48:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-12-011510.3389/fphar.2024.14597351459735Slick potassium channels limit TRPM3-mediated activation of sensory neuronsPatrick EngelFangyuan ZhouBang Tam Thi TranAchim SchmidtkoRuirui LuHeat sensation is mediated by specialized heat-sensitive neurons in the somatosensory system that innervates the skin. Previous studies revealed that noxious heat sensation is controlled by the sodium (Na+)-activated potassium (K+) channel Slick (Kcnt2), which is highly expressed in nociceptive Aδ-fibers. However, the mechanism by which Slick modulates heat sensation is poorly understood. Here, we generated mice lacking Slick conditionally in sensory neurons expressing Nav1.8 (SNS-Slick−/− mice). In SNS-Slick−/− mice, the latency to express any nocifensive behavior was reduced in the hot plate and tail immersion tests. In situ hybridization experiments revealed Slick was highly co-expressed with the essential heat sensor, transient receptor potential (TRP) melastatin (TRPM) 3, but not with TRP vanilloid 1, TRP ankyrin 1, or TRPM2 in sensory neurons. Notably, SNS-Slick−/− mice exhibited increased nocifensive behaviors following intraplantar injection of the TRPM3 activator pregnenolone sulfate. Patch-clamp recordings detected increased Na+-dependent outward K+ current (IK) after TRPM3 activation in sensory neurons, which showed no prominent IK after the replacement of NaCl with choline chloride. Thus, our study suggests that Slick limits TRPM3-mediated activation of sensory neurons, thereby inhibiting noxious heat sensing.https://www.frontiersin.org/articles/10.3389/fphar.2024.1459735/fullheat nociceptionTRPM3Slicksensory neuronspotassium current |
| spellingShingle | Patrick Engel Fangyuan Zhou Bang Tam Thi Tran Achim Schmidtko Ruirui Lu Slick potassium channels limit TRPM3-mediated activation of sensory neurons Frontiers in Pharmacology heat nociception TRPM3 Slick sensory neurons potassium current |
| title | Slick potassium channels limit TRPM3-mediated activation of sensory neurons |
| title_full | Slick potassium channels limit TRPM3-mediated activation of sensory neurons |
| title_fullStr | Slick potassium channels limit TRPM3-mediated activation of sensory neurons |
| title_full_unstemmed | Slick potassium channels limit TRPM3-mediated activation of sensory neurons |
| title_short | Slick potassium channels limit TRPM3-mediated activation of sensory neurons |
| title_sort | slick potassium channels limit trpm3 mediated activation of sensory neurons |
| topic | heat nociception TRPM3 Slick sensory neurons potassium current |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1459735/full |
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