{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:12:54Z","timestamp":1769577174862,"version":"3.49.0"},"reference-count":80,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T00:00:00Z","timestamp":1574208000000},"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":["31870770, 31271135"],"award-info":[{"award-number":["31870770, 31271135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Crosswise project","award":["53122-1371"],"award-info":[{"award-number":["53122-1371"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>It has been reported that Heteropodatoxin3 (HpTx3), a peptidic neurotoxin purified from the venom of the spider species Heteropoda venatoria, could inhibit Kv4.2 channels. Our present study newly found that HpTx3 also has potent and selective inhibitory action on Nav1.7, with an IC50 of 135.61 \u00b1 12.98 nM. Without effect on the current\u2013voltage (I-V) relationship of Nav1.7, HpTx3 made minor alternation in the voltage-dependence of activation and steady-state inactivation of Nav1.7 (4.15 mV and 7.29 mV, respectively) by interacting with the extracellular S3\u2013S4 loop (S3b\u2013S4 sequence) in domain II and the domain IV of the Nav channel subtype, showing the characteristics of both pore blocker and gate modifier toxin. During the interaction of HpTx3 with the S3b\u2013S4 sequence of Nav1.7, the amino acid residue D in the sequence played a key role. When administered intraperitoneally or intramuscularly, HpTx3 displayed potent analgesic activity in a dose-dependent manner in different mouse pain models induced by formalin, acetic acid, complete Freund\u2019s adjuvant, hot plate, or spared nerve injury, demonstrating that acute, inflammatory, and neuropathic pains were all effectively inhibited by the toxin. In most cases HpTx3 at doses of \u2265 1mg\/kg could produce the analgesic effect comparable to that of 1 mg\/kg morphine. These results suggest that HpTx3 not only can be used as a molecular probe to investigate ion channel function and pain mechanism, but also has potential in the development of the drugs that treat the Nav1.7 channel-related pain.<\/jats:p>","DOI":"10.3390\/toxins11120680","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T11:06:03Z","timestamp":1574247963000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Newly Discovered Action of HpTx3 from Venom of Heteropoda venatoria on Nav1.7 and Its Pharmacological Implications in Analgesia"],"prefix":"10.3390","volume":"11","author":[{"given":"Xinzhou","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhouquan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dehong","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2947-2741","authenticated-orcid":false,"given":"Xianchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1146\/annurev.physiol.63.1.871","article-title":"Resurgence of sodium channel research","volume":"63","author":"Goldin","year":"2001","journal-title":"Annu. 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