Bothriurus bonariensis scorpion venom activates voltage-dependent sodium channels in insect and mammalian nervous systems. (25th October 2016)

• Record Type: Journal Article
• Authors: dos Santos, Douglas Silva; Carvalho, Evelise Leis; de Lima, Jeferson Camargo; Breda, Ricardo Vaz; Oliveira, Raquel Soares; de Freitas, Thiago Carrazoni; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; Boldo, Juliano Tomazzoni; de Assis, Dênis Reis; da Costa, Jaderson Costa; Dal Belo, Cháriston André; Pinto, Paulo Marcos
• Is Part Of: Chemico-biological interactions. Volume 258(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-10-25
• Subjects: Arthropods -- Poison -- Neurotoxicity -- Neuromuscular blockade -- Calcium influx; BBV Bothirurus bonariensis venom -- 4-AP 4-aminopyridine -- TTX tetrodotoxin citrate -- DIV days in vitro -- HBS HEPES-buffered saline -- GLU glutamate -- SNCAP spontaneous neural compound action potentials -- NCX Na+/Ca2+ exchangers -- CaVs voltage-gated Ca2+ channels -- IP3 inositol triphosphate -- AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- CNS central nervous system -- PNS peripheral nervous system -- VGSC voltage-gated sodium channels; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2016.08.008
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Animal venoms have been widely recognized as a major source of biologically active molecules. Bothriurus bonariensis, popularly known as black scorpion, is the arthropod responsible for the highest number of accidents involving scorpion sting in Southern Brazil. Here we reported the first attempt to investigate the neurobiology of B. bonariensis venom (BBV) in the insect and mammalian nervous system. BBV (32 μg/g) induced a slow neuromuscular blockade in the in vivo cockroach nerve-muscle preparations (70 ± 4%, n = 6, p < 0.001), provoking repetitive twitches and significantly decreasing the frequency of spontaneous leg action potentials (SNCAPs) from 82 ± 3 min −1 to 36 ± 1.3 min −1 (n = 6, p < 0.05), without affecting the amplitude. When tested in primary cultures of rat hippocampal cells, BBV induced a massive increase of Ca 2+ influx (250 ± 1% peak increase, n = 3, p < 0.0001). The disturbance of calcium homeostasis induced by BBV on the mammalian central nervous system was not accompanied by cellular death and was prevented by the co-treatment of the hippocampal cells with tetrodotoxin, a selective sodium channel blocker. The results suggest that the biological activity of BBV is mostly related to a modulation of sodium channels function. Our biological activity survey suggests that BBV may have a promising insecticidal and therapeutic potential. Highlights: Bothirurus bonariensis venom (BBV) blocked cockroach nerve-muscle preparations. BBV caused a massive Ca 2+ influx in rat hippocampal cells. TTX prevented the effects of BBV in both cockroach preparations and rat cells. BBV may modulate voltage-dependent Na + channels. BBV constituents present biotechnological and therapeutic potential.