{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:53:07Z","timestamp":1787856787657,"version":"build-2784847793"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009594","name":"P\u00e9csi Tudom\u00e1nyegyetem","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Transient Receptor Potential (TRP) ion channels like Vanilloid 1 (TRPV1) and Melastatin 3 (TRPM3) are nonselective cation channels expressed in primary sensory neurons and peripheral nerve endings, which are located in cholesterol- and sphingolipid-rich membrane lipid raft regions and have important roles in pain processing. Besides TRP ion channels a wide variety of voltage-gated ion channels were also described in the membrane raft regions of neuronal cells. Here we investigated the effects of lipid raft disruption by methyl-beta-cyclodextrin (MCD) and sphingomyelinase (SMase) on TRPV1, TRPM3 and voltage-gated L-type Ca<jats:sup>2+<\/jats:sup> channel activation in cultured trigeminal neurons and sensory nerve terminals of the trachea. We also examined the mechanism of action of MCD by <jats:italic>in silico<\/jats:italic> modeling. Disruption of lipid rafts by MCD or SMase did not alter CIM0216-induced TRPM3 cation channel activation and the voltage-gated L-type Ca<jats:sup>2+<\/jats:sup> channel activation by FPL 64126 or veratridine neither on trigeminal sensory neurons nor sensory nerve terminals. We provided the first structural explanation with <jats:italic>in silico<\/jats:italic> modeling that the activation of TRPV1, TRPM3 and voltage-gated L-type Ca<jats:sup>2+<\/jats:sup> channels is affected differently by the cholesterol content surrounding them in the plasma membrane. It is concluded that modifying the hydrophobic interactions between lipid rafts and ion channels might provide a selective novel mechanism for peripheral analgesia.<\/jats:p>","DOI":"10.3389\/fcell.2024.1452306","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T07:09:30Z","timestamp":1732864170000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons"],"prefix":"10.3389","volume":"12","author":[{"given":"Maja","family":"Payrits","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs Zolt\u00e1n","family":"Zsid\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Kinga","family":"Nehr-Majoros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"B\u00f6rzsei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Het\u00e9nyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Sz\u0151ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/S13321-017-0255-6","article-title":"Systematic exploration of multiple drug binding sites","volume":"9","author":"B\u00e1lint","year":"2017","journal-title":"J. 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