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rickettsia and viruses, when they feed on blood, afflicting humans and other animals. Bioactive components acting on inflammation, coagulation, and the immune system were reported to facilitate ticks\u2019 ability to suck blood and transmit tick-borne diseases. In this study, a novel peptide, IstTx, from an Ixodes scapularis cDNA library was analyzed. The peptide IstTx, obtained by recombinant expression and purification, selectively inhibited a potassium channel, TREK-1, in a dose-dependent manner, with an IC50 of 23.46 \u00b1 0.22 \u03bcM. The peptide IstTx exhibited different characteristics from fluoxetine, and the possible interaction of the peptide IstTx binding to the channel was explored by molecular docking. Notably, extracellular acidification raised its inhibitory efficacy on the TREK-1 channel. Our results found that the tick-derived peptide IstTx blocked the TREK-1 channel and provided a novel tool acting on the potassium channel.<\/jats:p>","DOI":"10.3390\/ijms25158377","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:38:20Z","timestamp":1722515900000},"page":"8377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tick-Derived Peptide Blocks Potassium Channel TREK-1"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-9403","authenticated-orcid":false,"given":"Canwei","family":"Du","sequence":"first","affiliation":[{"name":"School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"},{"name":"College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchu","family":"Yuan","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqiang","family":"Rong","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, China"},{"name":"Frontiers Medical Center, Tianfu Jincheng Laboratory, No. 387-201 Heming Street, Chengdu 610212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Mo","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5627-2812","authenticated-orcid":false,"given":"Changjun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1017\/S0031182004005967","article-title":"The global importance of ticks","volume":"129","author":"Jongejan","year":"2004","journal-title":"Parasitology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mans, B.J., de Klerk, D., Pienaar, R., and Latif, A.A. 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