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001050295 1001_ $$0P:(DE-Juel1)194334$$aEicheldinger, Markus$$b0$$ufzj
001050295 245__ $$aCrotoxin B from the South American rattlesnake Crotalus vegrandisblocks voltage-gated calcium channels independent of its intrinsiccatalytic activity
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001050295 520__ $$aNeurotoxicity 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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001050295 7001_ $$0P:(DE-Juel1)180990$$aMiranda Laferte, Erick$$b1$$ufzj
001050295 7001_ $$0P:(DE-HGF)0$$aCastilla, Francisco$$b2
001050295 7001_ $$0P:(DE-Juel1)131932$$aJordan, Nadine$$b3$$ufzj
001050295 7001_ $$0P:(DE-Juel1)133853$$aSantiago-Schübel, Beatrix$$b4$$ufzj
001050295 7001_ $$0P:(DE-Juel1)151357$$aHidalgo, Patricia$$b5$$ufzj
001050295 773__ $$0PERI:(DE-600)2518395-3$$a10.3390/toxins18010036$$gVol. 18, no. 1, p. 36 -$$n1$$p18010036$$tToxins$$v18$$x2072-6651$$y2026
001050295 8564_ $$uhttps://juser.fz-juelich.de/record/1050295/files/Invoice_MDPI_toxins-3958594_2036.79EUR.pdf
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