6btv

Structural highlights

Function

[TX2_CERMR] Inhibits several voltage-gated sodium channels and only one voltage-gated calcium channel (Cav2.2/CACNA1B (IC(50)=1100 nM) and Nav1.2/SCN2A (IC(50)=8-80 nM), Nav1.3/SCN3A (88-5570 nM), Nav1.1/SCN1A (170-407 nM), Nav1.7/SCN9A (230 nM), Nav1.6/SCN6A (3990 nM), Nav1.4/SCN4A (400 nM or >10 uM), Nav1.5/SCN5A (1634 nM or >10 uM)) (PubMed:16267209, PubMed:28880874). The toxin acts by shifting the voltage dependence of channel activation to more depolarized potentials and by blocking the inward component of the sodium current (PubMed:16267209). In vivo, this toxin causes general ataxia, lack of response to stimuli, and semiparalysis (PubMed:16267209). After a few minutes, the mice are unable to stand, and breathing is reduced in rhythm and intensity (PubMed:16267209). Symptoms gradually increase with progressive slowing of breathing and flaccid paralysis; death occurred within 10 to 20 minutes post injection (PubMed:16267209). Animals remain totally flaccid, and no symptoms of excitatory neurotoxicity are observed (PubMed:16267209).^{[1] [2]}

References

1. ↑ Bosmans F, Rash L, Zhu S, Diochot S, Lazdunski M, Escoubas P, Tytgat J. Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes. Mol Pharmacol. 2006 Feb;69(2):419-29. Epub 2005 Nov 2. PMID:16267209 doi:http://dx.doi.org/mol.105.015941
2. ↑ Sousa SR, Wingerd JS, Brust A, Bladen C, Ragnarsson L, Herzig V, Deuis JR, Dutertre S, Vetter I, Zamponi GW, King GF, Alewood PF, Lewis RJ. Discovery and mode of action of a novel analgesic beta-toxin from the African spider Ceratogyrus darlingi. PLoS One. 2017 Sep 7;12(9):e0182848. doi: 10.1371/journal.pone.0182848., eCollection 2017. PMID:28880874 doi:http://dx.doi.org/10.1371/journal.pone.0182848