% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Eicheldinger:1050295,
      author       = {Eicheldinger, Markus and Miranda Laferte, Erick and
                      Castilla, Francisco and Jordan, Nadine and
                      Santiago-Schübel, Beatrix and Hidalgo, Patricia},
      title        = {{C}rotoxin {B} from the {S}outh {A}merican rattlesnake
                      {C}rotalus vegrandisblocks voltage-gated calcium channels
                      independent of its intrinsiccatalytic activity},
      journal      = {Toxins},
      volume       = {18},
      number       = {1},
      issn         = {2072-6651},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {FZJ-2026-00105},
      pages        = {18010036},
      year         = {2026},
      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.},
      cin          = {IBI-1},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBI-1-20200312},
      pnm          = {5243 - Information Processing in Distributed Systems
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5243},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.3390/toxins18010036},
      url          = {https://juser.fz-juelich.de/record/1050295},
}