{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:28:23Z","timestamp":1783488503928,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>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<jats:sup>+<\/jats:sup>)-activated potassium (K<jats:sup>+<\/jats:sup>) channel Slick (Kcnt2), which is highly expressed in nociceptive A\u03b4-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<jats:sup>\u2212\/\u2212<\/jats:sup> mice). In SNS-Slick<jats:sup>\u2212\/\u2212<\/jats:sup> mice, the latency to express any nocifensive behavior was reduced in the hot plate and tail immersion tests. <jats:italic>In situ<\/jats:italic> 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<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited increased nocifensive behaviors following intraplantar injection of the TRPM3 activator pregnenolone sulfate. Patch-clamp recordings detected increased Na<jats:sup>+<\/jats:sup>-dependent outward K<jats:sup>+<\/jats:sup> current (I<jats:sub>K<\/jats:sub>) after TRPM3 activation in sensory neurons, which showed no prominent I<jats:sub>K<\/jats:sub> 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.<\/jats:p>","DOI":"10.3389\/fphar.2024.1459735","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T04:22:39Z","timestamp":1734495759000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Slick potassium channels limit TRPM3-mediated activation of sensory neurons"],"prefix":"10.3389","volume":"15","author":[{"given":"Patrick","family":"Engel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang Tam Thi","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Schmidtko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/gene.20010","article-title":"Conditional gene deletion in primary nociceptive neurons of trigeminal ganglia and dorsal root ganglia","volume":"38","author":"Agarwal","year":"2004","journal-title":"Genesis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1097\/j.pain.0000000000002906","article-title":"TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain","volume":"164","author":"Aloi","year":"2023","journal-title":"Pain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1146\/annurev-pharmtox-010919-023238","article-title":"TRP channel cooperation for nociception: therapeutic opportunities","volume":"61","author":"Bamps","year":"2021","journal-title":"Annu. 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