Scorpions, cockroaches and clawed frogs may sound like ingredients in an ancient recipe for witches' brew. But bringing these animals together in a series of experiments has uncovered a new understanding of a more mundane problem: pesticide resistance in insects. The results of this recent study may help scientists to develop better pesticides—no spell book required.

Credit: Luis Carlos Jiménez del Río

Scorpions produce a variety of toxins that target different channels and receptors in their prey's neuromuscular systems. Common targets of these toxins are the voltage-gated sodium channels, proteins involved in rapid electrical signaling in nerve and muscle cells. Most organisms have a broad array of sodium channel variants with different specific properties, and some scorpion toxins selectively affect certain types of channels. For example, certain toxins are effective in insects but not in mammals. As a result, some of these toxins are valuable in the creation of insecticides. Unfortunately, over time, insects become resistant to toxins that target sodium channels. A research group led by Ke Dong (Michigan State University, East Lansing) set out to examine the mechanisms underlying the selectivity of scorpion toxin effects on insect sodium channels. Dong hopes the findings will help researchers to develop better insecticides and alternatives to control resistant pests. “Investigating the venom's effect on the voltage-gated sodium channel could provide valuable information for designing new insecticides that work by selectively targeting insect sodium channels,” he said in a press release.

First, the researchers isolated and produced a highly potent variant of an insect-selective toxin from the Israeli desert scorpion, Leiurus quinquestriatus hebraeus. Next, they engineered oocytes from clawed frogs (Xenopus) to express sodium channels from German cockroaches (Blattella germanica). They then investigated the interaction between the toxin and the sodium channel (J. Biol. Chem. 286, 15781–15788; 2011).

They identified one sodium channel variant that was extremely sensitive to the scorpion toxin. Comparing it with other less-sensitive variants, they found several amino acid changes in the channel's protein sequence that had affected its sensitivity to scorpion toxin. One of these changes, in the voltage-sensing module of domain III of the pore-forming α-subunit, was responsible for the hypersensitivity of this channel variant to scorpion toxin. Additionally, they found that changes to other specific amino acids in the channel's protein sequence increased the channel's toxin sensitivity. The results elucidate the mechanism underlying sodium channel sensitivity to scorpion toxin, information that could be exploited to produce more effective pesticides.