{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:06:58Z","timestamp":1785420418164,"version":"3.56.0"},"reference-count":93,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005298","name":"Universidad de Costa Rica","doi-asserted-by":"publisher","award":["C0-608"],"award-info":[{"award-number":["C0-608"]}],"id":[{"id":"10.13039\/501100005298","id-type":"DOI","asserted-by":"publisher"}]},{"award":["C0-608"],"award-info":[{"award-number":["C0-608"]}],"id":[{"id":"https:\/\/ror.org\/02yzgww51","id-type":"ROR","asserted-by":"publisher"}]},{"name":"FWO-Vlaanderen","award":["12W7822N"],"award-info":[{"award-number":["12W7822N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Scorpion neurotoxins are small peptides that target ion channels and offer opportunities for novel therapeutic discovery. This study analyzed the functional effects of the venom and toxins from the Costa Rican endemic scorpion, Tityus championi. Initially, crude venom was tested on different isoforms of voltage-gated sodium channels. Our findings revealed that the venom contains toxins that affect mammalian NaV1.6 and NaV1.7, as well as the cockroach BgNaV1 channel. Increased currents through NaV1.6 and BgNaV1 channels were associated with bigger window currents and inhibition of inactivation. Decreased NaV1.7 currents were associated with smaller conductance. Crude venom and TCh3 toxin inhibited action potential generation in invertebrate neurons expressing NaV1.7-like channels. In these neurons, Tch2 and Tch4 toxins shifted voltage sensitivity to more negative potentials, ultimately widening the window current but decreasing channel availability. Conversely, Tch3 behaved as an inhibitory toxin, closing window currents and decreasing channel availability. Structural modeling showed that Tch3 adopts an \u03b1\u03b2\u03b2 fold and binds the S3\u2013S4 loop of Domain II in human NaV1.7. These data show the diverse effects of scorpion venoms on channels and neurons, characterize its principal toxins, and show that Tch3 has therapeutic potential for pain relief.<\/jats:p>","DOI":"10.3390\/biom16040552","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T15:26:39Z","timestamp":1775661999000},"page":"552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Electrophysiological Characterization of the Venom and Toxins from the Scorpion Tityus championi Targeting Voltage-Gated Sodium Channels and Molecular Modeling of Tch3, a Toxin with Therapeutic Potential for Pain Relief"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-6566","authenticated-orcid":false,"given":"Galit","family":"Akerman-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Costa Rica, San Jos\u00e9 11501, Costa Rica"},{"name":"Postgraduate Study System, University of Costa Rica, San Jos\u00e9 11501, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-5702","authenticated-orcid":false,"given":"Steve","family":"Peigneur","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Carleer","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-473X","authenticated-orcid":false,"given":"Natalia","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Costa Rica, San Jos\u00e9 11501, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2943-7102","authenticated-orcid":false,"given":"Felipe","family":"Navia","sequence":"additional","affiliation":[{"name":"Laboratory of Herpetology and Toxinology, University of the Valley, Cali 760043, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Fierro","sequence":"additional","affiliation":[{"name":"Laboratory of Herpetology and Toxinology, University of the Valley, Cali 760043, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2758-8994","authenticated-orcid":false,"given":"Santiago","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Laboratory of Herpetology and Toxinology, University of the Valley, Cali 760043, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-9336","authenticated-orcid":false,"given":"Cecilia","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Costa Rica, San Jos\u00e9 11501, Costa Rica"},{"name":"Clodomiro Picado Institute, Faculty of Microbiology, University of Costa Rica, San Jos\u00e9 11103, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1778-6022","authenticated-orcid":false,"given":"Jan","family":"Tytgat","sequence":"additional","affiliation":[{"name":"Toxicology and Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven (KU Leuven), 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3830-9364","authenticated-orcid":false,"given":"Oscar","family":"Brenes","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Costa Rica, San Jos\u00e9 11501, Costa Rica"},{"name":"Neuroscience Research Center, University of Costa Rica, San Jos\u00e9 11501, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1046\/j.1440-1681.2002.03726.x","article-title":"Autonomic effects of some scorpion venoms and toxins","volume":"29","author":"Gwee","year":"2002","journal-title":"Clin. 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