Scorpion venom increases acetylcholine release by prolonging the duration of somatic nerve action potentials

Scorpionism is frequently accompanied by a massive release of catecholamines and acetylcholine from peripheral nerves caused by neurotoxic peptides present in these venoms, which have high specificity and affinity for ion channels. Tityus bahiensis is the second most medically important scorpion species in Brazil but, despite this, its venom remains scarcely studied, especially with regard to its pharmacology on the peripheral (somatic and autonomic) nervous system. Here, we evaluated the activity of T. bahiensis venom on somatic neurotransmission using myographic (chick and mouse neuromuscular preparations), electrophysiological (MEPP, EPP, resting membrane potentials, perineural waveforms, compound action potentials) and calcium imaging (on DRG neurons and muscle fibres) techniques. Our results show that the major toxic effects of T. bahiensis venom on neuromuscular function are presynaptically driven by the increase in evoked and spontaneous neurotransmitter release. Low venom concentrations prolong the axonal action potential, leading to a longer depolarization of the nerve terminals that enhances neurotransmitter release and facilitates nerve-evoked muscle contraction. The venom also stimulates the spontaneous release of neurotransmitters, probably through partial neuronal depolarization that allows calcium influx. Higher venom concentrations block the generation of action potentials and resulting muscle twitches. These effects of the venom were reversed by low concentrations of TTX, indicating voltage-gated sodium channels as the primary target of the venom toxins. These results suggest that the major neuromuscular toxicity of T. bahiensis venom is probably mediated mainly by α- and β-toxins interacting with presynaptic TTX-sensitive ion channels on both axons and nerve terminals

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

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

Neurotransmitter evaluation in the hippocampus of rats after intracerebral injection of TsTX scorpion toxin

TsTX is an a-type sodium channel toxin that stimulates the discharge of neurotransmitters from neurons. In the present study we investigated which neurotransmitters are released in the hippocampus after TsTX injection and if they are responsible for electrographic or histopathological effects. Microdialysis revealed that the toxin increased glutamate extracellular levels in the hippocampus; however, levels of gamma-aminobutyric acid (GABA), glycine, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were not significantly altered. Neurodegeneration in pyramidal cells of hippocampus and electroencephalographic alterations caused by the toxin were blocked by pretreatment with riluzole, a glutamate release inhibitor. The present results suggest a specific activity of TsTX in the hippocampus which affects only glutamate releas

Size-Dependent Morphology, Composition, Phase State, and Water Uptake of Nascent Submicrometer Sea Spray Aerosols during a Phytoplankton Bloom

The impact of sea spray aerosols (SSAs) on Earth’s climate remains uncertain in part due to size-dependent particle-to-particle variability in SSA physicochemical properties such as morphology, composition, phase state, and water uptake that can be further modulated by the environment relative humidity (RH). The current study investigates these properties as a function of particle size and RH, while focusing on submicrometer nascent SSA (0.1–0.6 μm) collected throughout a phytoplankton bloom. Filter-based thermal optical analysis, atomic force microscopy (AFM), and AFM photothermal infrared spectroscopy (AFM–PTIR) were utilized in this regard. AFM imaging at 20% RH identified five main SSA morphologies: prism-like, core–shell, rounded, rod, and aggregate. The majority of smaller SSAs throughout a bloom were rounded, while larger SSAs were core–shell. Filter-based measurements revealed an increasing organic mass fraction with decreasing SSA size. The organic matter is shown to primarily reside in a rounded and core–shell SSA, while the prism-like and rod SSA are predominantly inorganic salts (i.e., sodium chloride, nitrates, and sulfates) with relatively low organic content, as determined by AFM–PTIR spectroscopy. AFM phase state measurements at 20% RH revealed an increasing abundance of core–shell SSA with semisolid shells and rounded SSA with a solid phase state, as the particle size decreases. At 60% RH, shells of core–shell and rounded SSA uptake water, become less viscous, and their phase states change into either semisolid or liquid. Collectively, findings reveal the dynamic and size-dependent nature of SSA’s morphology, composition, phase states, and water uptake, which should be considered to accurately predict their climate-related effects