{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T11:27:17Z","timestamp":1768217237205,"version":"3.49.0"},"reference-count":70,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Neurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (CaV) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a non-covalent heterodimer formed by an acidic subunit (CA) and a basic toxic phospholipase A2 subunit (CB). Here, we chromatographically isolated the CB subunit from Crotalus vegrandis and studied its effect on CaV heterologously expressed in tsA201 cells using the whole-cell patch-clamp technique. Mass spectrometry analysis identified a protein that matched with 97% sequence coverage the CBc isoform from Crotalus durissus terrificus. Isolated CB exhibited moderate phospholipase activity that was not correlated to its cytotoxic effect on cultured tsA201 cells. Using Ba2+ as a charge carrier to prevent the enzymatic activity, we found that CB inhibited currents mediated by the N-type CaV2.2 and CaV1.2 L-type calcium channels, in a dose\u2013dependent manner, with higher potency for the latter, and negligible changes in the voltage dependence of channel activation. Our results reveal a novel phospholipase-independent biological activity and a molecular target of CB providing new insights into the pathophysiology of Crotalus snakebite envenoming with potential clinical therapeutic implications.<\/jats:p>","DOI":"10.3390\/toxins18010036","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:20:37Z","timestamp":1768206037000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Crotoxin B from the South American Rattlesnake Crotalus vegrandis Blocks Voltage-Gated Calcium Channels Independent of Its Intrinsic Catalytic Activity"],"prefix":"10.3390","volume":"18","author":[{"given":"Markus","family":"Eicheldinger","sequence":"first","affiliation":[{"name":"Institute of Biological Information Processing (IBI-1)\u2014Molecular and Cellular Physiology, Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-2673","authenticated-orcid":false,"given":"Erick","family":"Miranda-Laferte","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing (IBI-1)\u2014Molecular and Cellular Physiology, Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6057-5875","authenticated-orcid":false,"given":"Francisco","family":"Castilla","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing (IBI-1)\u2014Molecular and Cellular Physiology, Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8905-6566","authenticated-orcid":false,"given":"Nadine","family":"Jordan","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing (IBI-1)\u2014Molecular and Cellular Physiology, Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1762-9900","authenticated-orcid":false,"given":"Beatrix","family":"Santiago-Sch\u00fcbel","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing (IBI-7)\u2014Structural Biochemistry, Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4162-6590","authenticated-orcid":false,"given":"Patricia","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing (IBI-1)\u2014Molecular and Cellular Physiology, Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"},{"name":"Institute of Biochemistry, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.toxicon.2015.09.023","article-title":"Spencer, Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: Evidence of a broad arsenal of toxins","volume":"107","author":"Viala","year":"2015","journal-title":"Toxicon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0167-4838(01)00217-5","article-title":"Purification and characterisation of a haemorrhagic fraction from the venom of the Uracoan rattlesnake Crotalus vegrandis","volume":"1548","author":"Aguilar","year":"2001","journal-title":"Biochim. 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