Journal Article

FZJ-2026-00105

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Crotoxin B from the South American rattlesnake Crotalus vegrandisblocks voltage-gated calcium channels independent of its intrinsiccatalytic activity

Eicheldinger, M.FZJ* ; Miranda Laferte, E.FZJ* ; Castilla, F. ; Jordan, N.FZJ* ; Santiago-Schübel, B.FZJ* ; Hidalgo, P.FZJ*

2026
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/toxins18010036  doi:10.34734/FZJ-2026-00105

Abstract: 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–dependent 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.

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Contributing Institute(s):

1. Molekular- und Zellphysiologie (IBI-1)

Research Program(s):

1. 5243 - Information Processing in Distributed Systems (POF4-524) (POF4-524)

Appears in the scientific report 2026

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