Neurotoxicity ofTityus bahiensis(brown scorpion) venom in sympathetic vas deferens preparations and neuronal cells

Author(s)

Collaco, Rita de Cassia ^{[1, 2]} ; Hyslop, Stephen ^{[2, 3]} ; Rocha, Thalita ^[4] ; Dorce, Valquiria A. C. ^[5] ; Rowan, Edward G. ^[1] ; Antunes, Edson ^{[2, 3]}

Affiliation

^[1] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark - Scotland

^[2] State Univ Campinas UNICAMP, Dept Pharmacol, Fac Med Sci, Campinas, SP - Brazil

^[3] Dorce, Valquiria A. C., Butantan Inst, Div Sci Dev, Pharmacol Lab, Sao Paulo, SP, Brazil.Collaco, Rita de Cassia, State Univ Campinas UNICAMP, Dept Pharmacol, Fac Med Sci, Campinas, SP - Brazil

^[4] Sao Francisco Univ USF, Braganca Paulista, SP - Brazil

^[5] Butantan Inst, Div Sci Dev, Pharmacol Lab, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: ARCHIVES OF TOXICOLOGY; v. 94, n. 9 JUN 2020.
• Web of Science Citations: 0

Abstract

Systemic scorpion envenomation is characterized by massive neurotransmitter release from peripheral nerves mediated primarily by scorpion venoms neurotoxins.Tityus bahiensisis one of the medically most important species in Brazil, but its venom pharmacology, especially regarding to peripheral nervous system, is poorly understood. Here, we evaluated theT. bahiensisvenom activity on autonomic (sympathetic) neurotransmission by using a variety of approaches, including vas deferens twitch-tension recordings, electrophysiological measurements (resting membrane potentials, spontaneous excitatory junctional potentials and whole-cell patch-clamp), calcium imaging and histomorphological analysis. Low concentrations of venom (<= 3 mu g/mL) facilitated the electrically stimulated vas deferens contractions without affecting postsynaptic receptors or damaging the smooth muscle cells. Transient TTX-sensitive sustained contractions and resting membrane depolarization were mediated mainly by massive spontaneous ATP release. High venom concentrations (>= 10 mu g/mL) blocked the muscle contractions and induced membrane depolarization. In neuronal cells (ND7-23wt), the venom increased the peak sodium current, modified the current-voltage relationship by left-shifting the Na-v-channel activation curve, thereby facilitating the opening of these channels. The venom also caused a time-dependent increase in neuronal calcium influx. These results indicate that the sympathetic hyperstimulation observed in systemic envenomation is presynaptically driven, probably through the interaction of alpha- and beta-toxins with neuronal sodium channels. (AU)

• FAPESP's process: 16/11319-6 - The somatic and autonomic activities of Tityus bahiensis scorpion venom and its isolated fractions.
• Grantee: Rita de Cássia de Oliveira Collaço
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/23829-9 - Tityus bahiensis scorpion venom and its isolated fractions: an electrophysiological and calcium-imaging study on somatic and autonomic nerve-muscle systems.
• Grantee: Rita de Cássia de Oliveira Collaço
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate
• Grantee: Edson Antunes
• Support Opportunities: Research Projects - Thematic Grants