Scorpions sting over 250,000 people every year in Mexico alone. Most victims are lucky enough to survive if they get a dose of anti-venom in time, but several hundred still die every year because they can’t reach medical assistance. Scorpion venom is a cocktail of hundreds of individual toxins, which destroy the victim’s nervous system by targeting specific molecules in the nerve cells. Lourival Possani, working in Cuernavaca has discovered a completely new type of scorpion toxin that wrecks havoc by plugging the nerve’s essential sodium channels (p. 869).
Electrical signals flash along nerve cells when ion channels allow ions to flood into the cell, and then out again, as the nerves electric charge changes and the electrical signal moves along the cell. The ion channels select one of four ion types as the nerve cell fires.
Possani is particularly interested in the scorpion sting’s toxic ingredients and their fatal biochemistry. But each scorpion produces a vanishingly small amount of venom, so Possani collects stings from over 20,000 scorpions before he has enough of the lethal cocktail to separate the individual toxic components. Although a single scorpion’s sting will be deadly for many different species, each species will be targeted by a unique set of toxins from the mixture, and those same poisonous peptides may be completely inert in another species. Separating the individual components on the bases of the molecule’s size and charge, Possani is able to test which animal the toxin attacks, before finding out how it delivers its fatal blow.
Toxin Cn11 makes up less than two percent of a scorpion’s sting, but 15 μg is enough to kill an adult crayfish. Comparing the peptide’s sequence with other scorpion toxins, Possani realised that he was dealing with a toxin that interfered with the nerve’s sodium ion channels. But how was the toxin disrupting with channels behaviour? The only way to find out was by looking at a poisoned nerve’s dying signals.
Possani’s team turned to electrophysiology and recorded the electrical signal from entire crayfish nerve cells as they washed the neurons with Cn11. Because they measured the voltage of an entire cell, Possani’s team was looking at the sum of each sodium channel’s contribution to the nerve’s electrical signal. If the toxin was jamming the channel closed, small amounts of toxin would only shut a few channels, so the current would fall a little. But as they increased the amount of toxin, more channels would shut, dropping the current further, until he administered enough toxin to close every channel and completely shut the current off. Possani’s recordings proved that the he had unexpectedly found the first sodium channel blocker in scorpion toxin.
Possani is very excited. Cn11 is the first example of an entirely new class of toxin. A few other creatures have also developed sodium channel blockers, but they have very different structures and ways of blocking the ion channel. Although many technical challenges remain, Possani is optimistic that this toxic peptide could become a useful probe that might help us unravel the complicated structure of its victim; the sodium ion channel.