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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF TOXICOLOGY; v. 94, n. 9 JUN 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 16/11319-6 - Atividade do veneno de Tityus bahiensis e suas frações isoladas em preparações neuromusculares somáticas e autônoma.
• Beneficiário: Rita de Cássia de Oliveira Collaço
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/23829-9 - Veneno do Tityus bahiensis e suas frações isoladas: um estudo eletrofisiológico e de imagem de cálcio em preparações nervo-músculo do sistema nervoso somático e autonômico.
• Beneficiário: Rita de Cássia de Oliveira Collaço
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático