{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:41:30Z","timestamp":1789713690711,"version":"4.0.1"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T00:00:00Z","timestamp":1517529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670783"],"award-info":[{"award-number":["31670783"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573320"],"award-info":[{"award-number":["81573320"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31370854"],"award-info":[{"award-number":["31370854"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Jingzhaotoxin-34 (JZTX-34) is a selective inhibitor of tetrodotoxin-sensitive (TTX-S) sodium channels. In this study, we found that JZTX-34 selectively acted on Nav1.7 with little effect on other sodium channel subtypes including Nav1.5. If the DIIS3-S4 linker of Nav1.5 is substituted by the correspond linker of Nav1.7, the sensitivity of Nav1.5 to JZTX-34 extremely increases to 1.05 \u00b5M. Meanwhile, a mutant D816R in the DIIS3-S4 linker of Nav1.7 decreases binding affinity of Nav1.7 to JZTX-34 about 32-fold. The reverse mutant R800D at the corresponding position in Nav1.5 greatly increased its binding affinity to JZTX-34. This implies that JZTX-34 binds to DIIS3-S4 linker of Nav1.7 and the critical residue of Nav1.7 is D816. Unlike \u03b2-scorpion toxin trapping sodium channel in an open state, activity of JZTX-34 requires the sodium channel to be in a resting state. JZTX-34 exhibits an obvious analgesic effect in a rodent pain model. Especially, it shows a longer duration and is more effective than morphine in hot pain models. In a formalin-induced pain model, JZTX-34 at dose of 2 mg\/kg is equipotent with morphine (5 mg\/kg) in the first phase and several-fold more effective than morphine in second phase. Taken together, our data indicate that JZTX-34 releases pain by selectively binding to the domain II voltage sensor of Nav1.7 in a closed configuration.<\/jats:p>","DOI":"10.3390\/toxins10020064","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T06:45:40Z","timestamp":1517553940000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Selective Closed-State Nav1.7 Blocker JZTX-34 Exhibits Analgesic Effects against Pain"],"prefix":"10.3390","volume":"10","author":[{"given":"Xiongzhi","family":"Zeng","sequence":"first","affiliation":[{"name":"The National &amp; Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"},{"name":"The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Life Sciences College of Nanjing Agricultural University, 210095, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chen","sequence":"additional","affiliation":[{"name":"The National &amp; Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"},{"name":"The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Huang","sequence":"additional","affiliation":[{"name":"The National &amp; Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"},{"name":"The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Lai","sequence":"additional","affiliation":[{"name":"Life Sciences College of Nanjing Agricultural University, 210095, Jiangsu, China"},{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences &amp; Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingze","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqiang","family":"Rong","sequence":"additional","affiliation":[{"name":"The National &amp; Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"},{"name":"The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1517\/13543784.16.5.635","article-title":"Voltage-gated Na+ channels in neuropathic pain","volume":"16","author":"Hargus","year":"2007","journal-title":"Expert Opin. 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