Bark scorpion toxin loses its bite

B scorpion (Centruroides spp.) toxin is known to be intensely painful and potentially lethal. It provides the scorpion with a defence against predators; those that survive are unlikely to attack again. However, with grasshopper mice (Onychomys spp.) the toxin actually behaves as an analgesic. When stung, grasshopper mice will lick the wound for a few seconds before resuming the attack and devouring the scorpion. Recent research has elucidated some fascinating details of this phenomenon.1 There are multiple voltage-gated sodium (Na+) channels in mammals. One, known as Nav1.7, is the target of the toxin and initiates the pain signal that is then sent to the brain. At first it was suspected that changes to this protein would be responsible for the resistance of grasshopper mice to the toxin. After all, it was recently found that naked mole rats were insensitive to acid-induced pain because of amino acid differences in this protein. This allows them to live underground where there is a high concentration of carbon dioxide. However, researchers found that variation in a second Na+ channel, Nav1.8, is responsible for the unusual react ion of g rasshopper mice. Normally, Nav1.8 is responsible for transmitting signals of pain to the central nervous system. In grasshopper mice it binds to the bark scorpion toxin which blocks the signal of pain in a dose-dependent manner. In fact, after being exposed to the toxin, other painful stimuli, such as formalin, also have less of an effect. This was ascertained by measuring the amount of time spent licking the injection site after administration. Grasshopper mice have multiple amino acid variants in the Nav1.8 protein compared to house mice (Mus musculus). Those making a major contribution to venom sensitivity are localized in one region (domain II). In particular, the amino acids at positions 859 and 862 are switched. In grasshopper mice the hydrophilic glutamine (Q859) precedes the acidic glutamic acid (E862). The house mouse has the reverse (E859; Q862). The position of the acidic E862 appears essential to inhibit Na+ current, though the additional amino acid replacements may contribute as well. The researchers compared the residues at these two positions with those of Nav1.8 proteins in other rodents and non-rodent mammals. In all 18 species investigated, only glutamic acid (E) and glutamine (Q) were found. Seven of the 10 rodent species and one primate carried E862 which is critical for blocking Na+ current in grasshopper mice. Two of the rodents (Mesocricetus auratus, Cavia porcellus) and the primate (Otolemur garnetti) also carried Q859.