Abstract
Systemic scorpion envenomation is characterized by massive neurotransmitter release from peripheral nerves mediated primarily by scorpion venoms neurotoxins. Tityus bahiensis is 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 the T. bahiensis venom 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 μg/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 μg/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 Nav-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 α- and β-toxins with neuronal sodium channels.
Highlights
Scorpion envenomation is a major public health problem, especially in subtropical and tropical regions of developing countries (Chippaux 2012)
We have extended our study of the neurotoxicity of T. bahiensis venom to examine its actions on the sympathetic neurotransmission, using the vas deferens smooth muscle preparation, which is highly innervated by sympathetic nerve fibres and can be bisected onto epidydimal and prostatic portions (Burnstock and Verkhratsky 2010), representing a classical model of sympathetic co-transmission (ATP and noradrenaline)
Since the results described so far indicated that T. bahiensis venom acted on vas deferens mainly via presynaptic, TTXsensitive mechanisms, we examined the effect of the venom on sodium currents mediated by voltage-gated sodium N av 1.7, as this sodium channel subtype is responsible for 65% of the peak inward current, followed by Nav1.6 (∼20%) in ND7-23 wt cells (Rogers et al 2016)
Summary
Scorpion envenomation is a major public health problem, especially in subtropical and tropical regions of developing countries (Chippaux 2012). The clinical manifestations of envenoming by Tityus spp. are mostly local, consisting of immediate severe pain and varying degrees of erythema, edema and paraesthesia (Bucaretchi et al 2014; Cupo 2015). Systemic envenomation by Tityus spp. frequently results in an ‘autonomic storm’ that consists of a massive release of sympathetic and parasympathetic neurotransmitters that leads to a complex pattern of central and peripheral responses. The parasympathetic stimulation occurs immediately after the sting and tends to be less severe than the sympathetic stimulation, which is persistent and responsible for most lethal effects observed in the later stages of systemic envenomation (Bucaretchi et al 2014; Isbister and Bawaskar 2014). The “autonomic storm” on systemic scorpionism is commonly attributed to the action of neurotoxic peptides that modulate ion channel activity and, neurotransmitter release (Guieu et al 1995; Lourenço et al 2002; Pucca et al 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
