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Neurotoxicity of Tityus bahiensis (brown scorpion) venom in sympathetic vas deferens preparations and neuronal cells.
Archives of Toxicology ( IF 4.8 ) Pub Date : 2020-06-16 , DOI: 10.1007/s00204-020-02799-y
Rita de Cássia Collaço 1, 2 , Stephen Hyslop 1 , Thalita Rocha 3 , Valquiria A C Dorce 4 , Edward G Rowan 2 , Edson Antunes 1
Affiliation  

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.



中文翻译:

Tityus bahiensis(棕蝎子)毒液对交感输精管制剂和神经元细胞的神经毒性。

全身性蝎毒中毒的特点是周围神经释放大量神经递质,主要由蝎毒神经毒素介导。Tityus bahiensis是巴西医学上最重要的物种之一,但其毒液药理学,尤其是与周围神经系统有关的药理学,人们却知之甚少。在这里,我们通过使用多种方法评估了巴希金龟毒液对自主(交感)神经传递的活性,包括输精管抽搐张力记录、电生理测量(静息膜电位、自发兴奋性连接电位和全细胞膜片钳) 、钙成像和组织形态学分析。低浓度的毒液(≤ 3 μg/mL)促进电刺激输精管收缩,而不影响突触后受体或损害平滑肌细胞。瞬时 TTX 敏感的持续收缩和静息膜去极化主要由大量自发 ATP 释放介导。高毒液浓度(≥ 10 μg/mL)会阻止肌肉收缩并诱导膜去极化。在神经元细胞 (ND7-23 wt ) 中,毒液增加了峰值钠电流,通过左移 Na v通道激活曲线来修改电流-电压关系,从而促进这些通道的打开。毒液还引起神经元钙流入的时间依赖性增加。这些结果表明,在全身毒液中观察到的交感神经过度刺激是突触前驱动的,可能是通过α-和β-毒素与神经元钠通道的相互作用来驱动的。

更新日期:2020-06-16
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