Hauptseite > Publikationsdatenbank > Crotoxin B from the South American rattlesnake Crotalus vegrandisblocks voltage-gated calcium channels independent of its intrinsiccatalytic activity > print

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100 1 _ |a Eicheldinger, Markus
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245 _ _ |a Crotoxin B from the South American rattlesnake Crotalus vegrandisblocks voltage-gated calcium channels independent of its intrinsiccatalytic activity
260 _ _ |a Basel
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520 _ _ |a 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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700 1 _ |a Castilla, Francisco
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700 1 _ |a Santiago-Schübel, Beatrix
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700 1 _ |a Hidalgo, Patricia
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773 _ _ |a 10.3390/toxins18010036
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856 4 _ |u https://juser.fz-juelich.de/record/1050295/files/Invoice_MDPI_toxins-3958594_2036.79EUR.pdf
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