TY  - JOUR
AU  - Eicheldinger, Markus
AU  - Miranda Laferte, Erick
AU  - Castilla, Francisco
AU  - Jordan, Nadine
AU  - Santiago-Schübel, Beatrix
AU  - Hidalgo, Patricia
TI  - Crotoxin B from the South American rattlesnake Crotalus vegrandisblocks voltage-gated calcium channels independent of its intrinsiccatalytic activity
JO  - Toxins
VL  - 18
IS  - 1
SN  - 2072-6651
CY  - Basel
PB  - MDPI
M1  - FZJ-2026-00105
SP  - 18010036
PY  - 2026
AB  - 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.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.3390/toxins18010036
UR  - https://juser.fz-juelich.de/record/1050295
ER  -