https://m2.mtmt.hu/ hun 2026-05-30 16:04 JournalArticle 33262968 VALIDATED true Hungarian Centre of Excellence for Molecular Medicine-Semmelweis Egyetem (HCEMM-SE), Molecular Channelopathies Research Group, Semmelweis University, Budapest, H-1094, Hungary Magyar Tudományos Akadémia-Semmelweis Egyetem (MTA-SE), Ion Channel Research Group, Semmelweis University, Budapest, H-1094, Hungary Department of Biochemistry, Semmelweis University, Budapest, H-1094, Hungary Cited By :3 Export Date: 4 September 2023 CODEN: PNASA Correspondence Address: Csanády, L.; Hungarian Centre of Excellence for Molecular Medicine-Semmelweis Egyetem (HCEMM-SE), Hungary; email: csanady.laszlo@med.semmelweis-univ.hu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium ion, 14127-61-8; hydrogen peroxide, 7722-84-1; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; Hydrogen Peroxide; TRPM Cation Channels Funding details: 739593 Funding details: GINOP-2.3.2-15-2016-00051 Funding details: ÚNKP-20-5-SE-6, ÚNKP-21-5-SE-10 Funding details: Magyar Tudományos Akadémia, MTA, BO/00103/20, LP2017-14/2017 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding text 1: We thank Beáta Töröcsik for subcloning T5L-TRPM2 into pcDNA3, Iordan Iordanov for providing purified nvNUDT9H, and Katalin Zboray (Agricultural Institute, Centre for Agricultural Research, Martonvásár, Hungary) for providing the stable T5L TRPM2 cell line (Economic Development and Innovation Operational Programme (GINOP-2.3.2-15-2016-00051) of the National Research, Development and Innovation Office). Support was provided by EU Horizon 2020 Research and Innovation Program grant 739593 and MTA Lendület grant LP2017-14/2017 to L.C. and a New National Excellence Program (ÚNKP) award of the Ministry of Human Capacities of Hungary to Semmelweis University. Á.B. was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20) and the New National Excellence Program (ÚNKP) Bolyai+ scholarship of the Ministry of Human Capacities of Hungary (ÚNKP-20-5-SE-6 and ÚNKP-21-5-SE-10). Funding text 2: ACKNOWLEDGMENTS. We thank Beáta Töröcsik for subcloning T5L-TRPM2 into pcDNA3, Iordan Iordanov for providing purified nvNUDT9H, and Katalin Zboray (Agricultural Institute, Centre for Agricultural Research, Martonvásár, Hungary) for providing the stableT5LTRPM2 cell line (Economic Development and Innovation Operational Programme (GINOP-2.3.2-15-2016-00051) of the National Research, Development and Innovation Office). Support was provided by EU Horizon 2020 Research and Innovation Program grant 739593 and MTA Lendület grant LP2017-14/2017 to L.C. and a New National Excellence Program (ÚNKP) award of the Ministry of Human Capacities of Hungary to Semmelweis University. Á.B. was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20) and the New National Excellence Program (ÚNKP) Bolyai+ scholarship of the Ministry of Human Capacities of Hungary (ÚNKP-20-5-SE-6 and ÚNKP-21-5-SE-10). 0 false 2026-05-28T08:04:39.316+0000 2023-12-06T07:48:23.478+0000 2022-11-23T10:14:13.664+0000 true 10034486 Bartók Ádám /api/author/10034486 Author true 10034486 2026-04-30T09:09:19.807+0000 2023-12-06T07:48:23.923+0000 true 10080205 Szalóky-Siki Ágnes /api/admin/10080205 Admin true Admin 10003134 /api/admin/10003134 Wolf György true 10003134 true Admin 10067876 /api/admin/10067876 Ladányi Gusztáv true true 2024-10-17T16:09:40.962+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Bartók, Ádám Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors true true /api/journal/3547 REVIEWED true false 3547 false 3547 true 0027-8424 1091-6490 Journal FOREIGN 119 48 e2212378119 e2212378119 11 2022 The Ca 2+ and ADP ribose (ADPR)-activated cation channel TRPM2 is the closest homolog of the cold sensor TRPM8 but serves as a deep-brain warmth sensor. To unravel the molecular mechanism of heat sensing by the TRPM2 protein, we study here temperature dependence of TRPM2 currents in cell-free membrane patches across ranges of agonist concentrations. We find that channel gating remains strictly agonist-dependent even at 40°C: heating alone or in combination with just Ca 2+ , just ADPR, Ca 2+ + cyclic ADPR, or H 2 O 2 pretreatment only marginally activates TRPM2. For fully liganded TRPM2, pore opening is intrinsically endothermic, due to ~10-fold larger activation enthalpy for opening (~200 kJ/mol) than for closure (~20 kJ/mol). However, the temperature threshold is too high (>40°C) for unliganded but too low (<15°C) for fully liganded channels. Thus, warmth sensitivity around 37°C is restricted to narrow ranges of agonist concentrations. For ADPR, that range matches, but for Ca 2+ , it exceeds bulk cytosolic values. The supraphysiological [Ca 2+ ] needed for TRPM2 warmth sensitivity is provided by Ca 2+ entering through the channel’s pore. That positive feedback provides further strong amplification to the TRPM2 temperature response (Q 10 ~ 1,000), enabling the TRPM2 protein to autonomously respond to tiny temperature fluctuations around 37°C. 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<span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Biokémiai és Molekuláris Biológiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Biokémiai Tanszék; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/ELKH-SE Ioncsatorna Kutatócsoport; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/HCEMM-SE Molekuláris Csatornabetegségek Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10015499"><a href="/gui2/?type=authors&mode=browse&sel=10015499" target="_blank">Csanády László ✉ (<span class="authorship-author-name">Csanády László</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/MTA-SE Lendület Ioncsatorna Kutatócsoport; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Biokémiai és Molekuláris Biológiai Intézet; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Biokémiai Tanszék; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/ELKH-SE Ioncsatorna Kutatócsoport; <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/<span title="Biokémiai Tanszék">BT</span>/HCEMM-SE Molekuláris Csatornabetegségek Kutatócsoport</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;33262968" target="_blank">Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors</a></div> <div> <span class="journal-title">PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0027-8424">0027-8424</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1091-6490">1091-6490</a>)</span>: <span class="journal-volume">119</span> <span class="journal-issue">48</span> <span class="page"> Paper e2212378119. 11 p. </span> <span class="year">(2022)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1073/pnas.2212378119" target="_blank" href="https://doi.org/10.1073/pnas.2212378119"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000929044100021" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000929044100021"> WoS </a> </span> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:black" title="172937" target="_blank" href="http://real.mtak.hu/172937"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85142398706" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85142398706"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="36409885" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=36409885&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_NONE" title=" Nincs "> <a style="color:blue" title="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142398706&doi=10.1073%2Fpnas.2212378119&partnerID=40&md5=9d7f63ca900b1ddc4b52da0490bf85c7" target="_blank" href="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142398706&doi=10.1073%2Fpnas.2212378119&partnerID=40&md5=9d7f63ca900b1ddc4b52da0490bf85c7"> Egyéb URL </a> </span> <span class="id identifier oa_NONE" title=" Nincs "> <a style="color:blue" title="https://www.scopus.com/pages/publications/85142398706?origin=resultslist" target="_blank" href="https://www.scopus.com/pages/publications/85142398706?origin=resultslist"> Egyéb URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Multidisciplinary&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">X. 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