Differential effects of five ‘classical’ scorpion β-toxins on rNav1.2a and DmNav1 provide clues on species-selectivity

Abstract

In general, scorpion β-toxins have been well examined. However, few in-depth studies have been devoted to species selectivity and affinity comparisons on the different voltage-activated Na + channels since they have become available as cloned channels that can be studied in heterologous expression systems. As a result, their classification is largely historical and dates from early in vivo experiments on mice and cockroach and fly larvae.In this study, we aimed to provide an updated overview of selectivity and affinity of scorpion β-toxins towards voltage-activated Na + channels of vertebrates or invertebrates. As pharmacological tools, we used the classic β-toxins AaHIT, Css II, Css IV, Css VI and Ts VII and tested them on the neuronal vertebrate voltage-activated Na + channel, rNa v 1.2a. For comparison, its invertebrate counterpart, DmNav1, was also tested. Both these channels were expressed in Xenopus laevis oocytes and the currents measured with the two-electrode voltage-clamp technique. We supplemented this data with several binding displacement studies on rat brain synaptosomes. The results lead us to propose a general classification and a novel nomenclature of scorpion β-toxins based on pharmacological activity.

Effects of BmK AS on Nav1.2 expressed in Xenopus laevis oocytes

“…It is noticed that the little effects of BmK AS on the activation process of expressed rNav1.2 α-subunits was different from a drastic hyperpolarizing shift, which another β-like scorpion toxin Ts VII recorded on expressed rNav1.2α/β (Bosmans et al 2007). It might be attributed to three possibilities: Firstly, our active protocol lack a pre-pulse, but it might not be essential because a pre-pulse had tried during prior experiments with a slight change (data not shown).…”

Poison Frog Colors Are Honest Signals of Toxicity, Particularly for Bird Predators

“…Dendrobatids, like many other organisms that use toxins for defense, such as birds (Dumbacher et al 1992), scorpions (Bosmans et al 2007), spiders (Szelistowski 1985;Gray et al 2010), and ants (Fritz et al 1981), use alkaloid compounds that target voltage-gated ion channels (Daly et al 1980;Daly 1998;Bosmans et al 2004). Because ion channels are fundamental components of nervous systems across invertebrate and vertebrate taxa, this is a generalized defense.…”

Scorpion toxin peptide action at the ion channel subunit level

“…Some identified peptides demonstrated the ability to discriminate between mammalian and nonmammalian channel subtypes. For example, AaHIT (Androctonus australis Hector) (Bosmans et al, 2007) and BjaIT (Buthotus judaicus) (Arnon et al, 2005) were highly selective against insect channel orthologues. In contrast Css VI (Centruroides suffusus suffusus) affected rat Nav1.2 at 5 mM, but did not affect DMNaV1 (Bosmans et al, 2007).…”

“…For example, AaHIT (Androctonus australis Hector) (Bosmans et al, 2007) and BjaIT (Buthotus judaicus) (Arnon et al, 2005) were highly selective against insect channel orthologues. In contrast Css VI (Centruroides suffusus suffusus) affected rat Nav1.2 at 5 mM, but did not affect DMNaV1 (Bosmans et al, 2007). Such differences are likely to be due to differences in ion channel amino acid sequence affecting the site of toxin action.…”

“…Buthus martensii Karsch Increased current, Human, CHO cells, 100 pM, (Meng et al, 2015) Increased current, Human, CHO, 100 pM, (Meng et al, 2015 Peptide Species DmNav1 (Para) Nav1.1 Nav1.2 Nav1.3 Nav1.4 Nav1.5 Nav1.6 Nav1.7 Nav1.8 5 mM, (Bosmans et al, 2007) 5 mM, (Bosmans et al, 2007 (Rowe et al, 2011) Inhibit fast inactivation, Rat, HEK293, 1 mM, (Rowe et al, 2011) Inhibit fast inactivation, Rat, HEK293, 1 mM, (Rowe et al, 2011) Inhibit fast inactivation, Human, HEK293, 1 mM, (Rowe et al, 2011) Kbot55a-Ktx31.1…”